Bacterial Mucosal Immunotherapy with MV130 Prevents Recurrent Wheezing in Children: A Randomized, Double-Blind, Placebo-controlled Clinical Trial.

Rationale: Recurrent wheezing in children represents a severe public health concern. Wheezing attacks (WA), mainly associated with viral infections, lack effective preventive therapies. Objectives: To evaluate the efficacy and safety of mucosal sublingual immunotherapy based on whole inactivated bacteria (MV130) in preventing WA in children. Methods: A Phase 3 randomized, double-blind, placebo-controlled, parallel-group trial including a cohort of 120 children <3 years old with ⩾3 WA during the previous year was conducted. Children with a positive skin test to common aeroallergens in the area where the clinical trial was performed were excluded from the trial. Subjects received MV130 or placebo daily for 6 months. The primary endpoint was the number of WA within 1 year after the first dose comparing MV130 and placebo. Measurements and Main Results: There was a significant lower number of WA in MV130 versus the placebo group, 3.0 (interquartile range [IQR], 2.0-4.0) versus 5.0 (IQR, 3.0-7.0) (P < 0.001). As secondary outcomes, a decrease in the duration of WA and a reduction in symptoms and medication scores in the MV130 versus placebo group were found. No adverse events were reported related to the active treatment. Conclusions: Mucosal bacterial immunotherapy with MV130 shows safety and clinical efficacy against recurrent WA in children.Clinical trial registered with www.clinicaltrials.gov (NCT01734811).

Quantitative assessments reveal improved neuroscience engagement and learning through outreach.

Lack of resources and exposure to neuroscience in K-12 education has resulted in a limited number of K-12 students pursuing higher education in the field. Meanwhile, the rapid expansion of the field of neuroscience has encouraged many higher educational institutes to offer neuroscience majors. This has opened up the opportunity to engage faculty, as well as graduate and undergraduate students in bringing the most needed knowledge and awareness about neuroscience into K-12 classrooms. However, undergraduate neuroscience curricula have limited formal opportunities to engage in outreach, and few existing programs have assessments to determine their effectiveness. To address these needs, we developed quantitative assessment tools that complement an existing neuroscience outreach program-Project Brainstorm-at the University of California, Los Angeles (UCLA). 29 UCLA undergraduates enrolled in the 2016 and 2017 programs participated in this study, along with 298 K-12 students from local schools across the Los Angeles area. In undergraduate students, we assessed (a) improvement in students' teaching/communication abilities across the course of the outreach program, and (b) confidence in explaining neuroscience topics and interest in pursuing teaching career. In K-12 students, we evaluated (a) knowledge gain in neuroscience topics and (b) interest in pursuing higher education. Overall, Project Brainstorm showed significant improvement in all the above-mentioned categories. The assessment tools and data presented here provide a data-driven approach for optimizing neuroscience outreach programs and can easily be adapted to other outreach programs within neuroscience and in other STEM fields.

Complexation and Electronic Communication between Corannulene-Based Buckybowls and a Curved Truxene-TTF Donor.

The association behavior of an electron-donating, bowl-shaped, truxene-based tetrathiafulvalene (truxTTF) with two corannulene-based fullerene fragments, C32 H12 and C38 H14 , is investigated in several solvents. Formation of 1:1 complexes is followed by absorption titrations and complemented by density functional theory (DFT) calculations. The binding constants are in the range log Ka =2.9-3.5. DFT calculations reveal that the most stable arrangement is the conformation in which the 1,3-dithiole ring of truxTTF is placed inside the concave cavity of the corannulene derivative. This arrangement is confirmed experimentally by NMR measurements, and implies that a combination of π-π and CH-π interactions is the driving force for association. Time-dependent DFT calculations reproduce the experimental UV/Vis titrations and provide a detailed understanding of the spectral changes observed. Femtosecond transient absorption studies reveal the processes occurring after photoexcitation of either C32 H12 or C38 H14 and their supramolecular associates with truxTTF. In the case of truxTTF⋅C38 H14 , photoexcitation yields the charge-separated state truxTTF.+ ⋅C38 H14.- with a lifetime of approximately 160 ps.

Phthalocyanine-Perylenediimide Cart Wheels.

The electronic features of Zn(II) and Ru(II) phthalocyanines (Pcs) have been modulated by direct peripheral attachment of up to eight ferrocenes. The presence of peripheral ferrocenes noticeably impacts the electronic properties of the corresponding ZnPc and RuPc complexes 7, 12 and 9, 15, respectively-a notion that is supported by optical spectroscopy with bathochromic shifts of up to 8-10 nm per ferrocene unit. Cyclic voltammetry and optical spectroscopy reveal long-distance (10-11 bonds) electronic interaction between ferrocene units. The ZnPc and RuPc complexes have been integrated into a series of orthogonal, supramolecular bis(phthalocyanine)-perylenediimide electron donor-acceptor conjugates, 2a,b and 3a,b. In these cart-wheel-shaped arrays, coordination of ditopic perylenediimide 16, containing two pyridyl substituents at its imido positions, enabled selective interactions with the metal centers of phthalocyanines 7, 12, 9, and 15. The presence of ferrocenes in, for example, Zn complexes 2a and 3a triggers a fast energy transfer from the excited-state PDI to ZnPc. In the RuPc-PDI conjugates, substitution with ferrocenes produces a slight acceleration of the charge separation upon photoexcitation of the PDI chromophore. However, charge recombination is accelerated by 2 orders of magnitude in ferrocene-containing conjugates when compared to that in the analogous tert-butyl-substituted array 1b.

Enhancing molecular recognition in electron donor-acceptor hybrids via cooperativity.

Herein, we report the synthesis of guanidinium bis-porphyrin tweezers 1 and fullerene carboxylate 3, their assembly into a novel supramolecular 1@3 electron donor-acceptor hybrid, and its characterization. In solution, the binding constant affording 1@3 is exceptionally high. 1@3, which features a highly confined topography, builds up from a combination of guanidinium-carboxylate hydrogen bonding and π-π stacking/charge-transfer motifs. The latter is governed by interactions between the electron-donating porphyrin and the electron-accepting fullerene. Importantly, positive cooperativity between the applied binding motifs is corroborated by a number of experimental techniques, such as NMR, absorption, fluorescence, etc. In addition, transient absorption experiments shed light onto electron-transfer processes taking place in the ground state and upon photoexcitation. In fact, porphyrin excitation powers an electron transfer to the fullerene yielding charge separated state lifetimes in the nanosecond regime.

Electron transfer in a supramolecular associate of a fullerene fragment.

Herein, we investigate the association of a fullerene fragment, hemifullerene C30H12, with an electron-donating bowl-shaped tetrathiafulvalene derivative (truxTTF). UV/Vis titrations and DFT calculations support formation of the supramolecular complex, for which an association constant of log Ka = 3.6±0.3 in CHCl3 at room temperature is calculated. Remarkably, electron transfer from truxTTF to C30H12 to form the fully charge-separated species takes place upon irradiation of the associate with light, constituting the first example in which a fullerene fragment mimics the electron-accepting behavior of fullerenes within a supramolecular complex.

Increasing Accessibility to Neuroscience through Translation: Going beyond the English Language.

Declaring the 1990s as The Decade of the Brain put the field of neuroscience at the forefront of public attention, with the nervous system becoming a subject of increasing interest in popular media. Although this has generally brought large swaths of the public closer to neuroscience, most current research is published and disseminated in a single language: English. This is unsurprising as English is indeed the lingua franca in scientific circles, but people around the world communicate in many other languages. To make neuroscience accessible to a larger audience, we share an initiative to translate the Knowing Neurons platform into a second language: Spanish. This collaborative project integrates humanities and STEM academic programs to make use of bilingual university students, in association with professional linguists and neuroscientists, to translate scientific content into a relatable format to Spanish speakers regardless of their country of origin. The translation effort was piloted within the framework of undergraduate outreach courses at the University of California, Los Angeles, and is coupled with outreach components targeting the Spanish-speaking community to promote this new resource. This project aims to foster an environment where the neuroscientific interests of the public, college students, instructors, and researchers coalesce in a unified space. We hope that opening new lines of communication with traditionally underrepresented communities might help combat the persistent lack of diversity in neuroscience (and STEM) that is currently seen in academia. We also provide an outline to inspire others to translate these, and similar resources, into other languages.

First large-scale study reveals important losses of managed honey bee and stingless bee colonies in Latin America.

Over the last quarter century, increasing honey bee colony losses motivated standardized large-scale surveys of managed honey bees (Apis mellifera), particularly in Europe and the United States. Here we present the first large-scale standardized survey of colony losses of managed honey bees and stingless bees across Latin America. Overall, 1736 beekeepers and 165 meliponiculturists participated in the 2-year survey (2016-2017 and 2017-2018). On average, 30.4% of honey bee colonies and 39.6% of stingless bee colonies were lost per year across the region. Summer losses were higher than winter losses in stingless bees (30.9% and 22.2%, respectively) but not in honey bees (18.8% and 20.6%, respectively). Colony loss increased with operation size during the summer in both honey bees and stingless bees and decreased with operation size during the winter in stingless bees. Furthermore, losses differed significantly between countries and across years for both beekeepers and meliponiculturists. Overall, winter losses of honey bee colonies in Latin America (20.6%) position this region between Europe (12.5%) and the United States (40.4%). These results highlight the magnitude of bee colony losses occurring in the region and suggest difficulties in maintaining overall colony health and economic survival for beekeepers and meliponiculturists.

Self-assembly, host-guest chemistry, and photophysical properties of subphthalocyanine-based metallosupramolecular capsules.

Four new subphthalocyanine-based capsules have been synthesized and characterized. These supramolecular systems have been successfully employed for the encapsulation of fullerenes and probed by a wide range of characterization methods, including NMR, UV-vis and fluorescence spectroscopy, electrospray ionization mass spectrometry, and electrochemistry. Furthermore, the binding constants of the host guest complexes were estimated. Finally, the photophysical properties revealed that the subphthalocyanines undergo a transduction of singlet excited-state energy to the fullerene inside the cavity upon photoexcitation.

Cardiac amyloidosis secondary to multiple myeloma.

Amyloidosis is a multisystemic disease caused by extracellular deposition of pathologic beta fibrillar proteins in multiple organs. Deposited fibrils can be either innunoglobulin light chanis or amyloid-A protein. The incidence of anyloidosis derived from anyloid-A protein, usually associated to an underlying disease, has been dimisishing over the decades in the United States producing clinical evidence of cardiac involvement in less than 5% of all cases. The extent of cardiac involvement is the determining prognostic factor. Early diagnosis and therapy aimed at the underlying disease may halt progression of cardiac dysfuction and improve prognosis. We report a case of a 63-year-old man who was diagnosed with cardiac amyloidosis secondary to multiple myeloma.

Observation of Varroa destructor behavior in capped worker brood of Africanized honey bees.

The behavioral activity of Varroa destructor was observed using transparent cells. Mite oviposition started at 45.0 ± 25.0 h post capping, followed by the next eggs laid at regular 27.3 ± 2.0 h intervals. On the prepupa, mites were found to feed often and there was no preference for a specific segment as a feeding site. During the pupal stage the mite fed less often and almost always at the same point. Varroa showed a preference for defecation in the posterior part of the cell. A significant association was observed between the position of the feeding point in the pupa and the defecation site on the cell wall. Displacement behavior was observed in 71 % of the infested bee larvae and a major change in the free space available for varroa in the cell occurred when the prepupa molted into a pupa.

A photochemical on-off switch for tuning the equilibrium mixture of H2 nuclear spin isomers as a function of temperature.

The photochemical interconversion of the two allotropes of the hydrogen molecule [para-H(2) (pH(2)) and ortho-H(2) (oH(2))] incarcerated inside the fullerene C(70) (pH(2)@C(70) and oH(2)@C(70), respectively) is reported. Photoexcitation of H(2)@C(70) generates a fullerene triplet state that serves as a spin catalyst for pH(2)/oH(2) conversion. This method provides a means of changing the pH(2)/oH(2) ratio inside C(70) by simply irradiating H(2)@C(70) at different temperatures, since the equilibrium ratio is temperature-dependent and the electronic triplet state of the fullerene produced by absorption of the photon serves as an "on-off" spin catalyst. However, under comparable conditions, no photolytic pH(2)/oH(2) interconversion was observed for H(2)@C(60), which was rationalized by the significantly shorter triplet lifetime of H(2)@C(60) relative to H(2)@C(70).

A glial variant of the vesicular monoamine transporter is required to store histamine in the Drosophila visual system.

Unlike other monoamine neurotransmitters, the mechanism by which the brain's histamine content is regulated remains unclear. In mammals, vesicular monoamine transporters (VMATs) are expressed exclusively in neurons and mediate the storage of histamine and other monoamines. We have studied the visual system of Drosophila melanogaster in which histamine is the primary neurotransmitter released from photoreceptor cells. We report here that a novel mRNA splice variant of Drosophila VMAT (DVMAT-B) is expressed not in neurons but rather in a small subset of glia in the lamina of the fly's optic lobe. Histamine contents are reduced by mutation of dVMAT, but can be partially restored by specifically expressing DVMAT-B in glia. Our results suggest a novel role for a monoamine transporter in glia that may be relevant to histamine homeostasis in other systems.

Aborted sudden cardiac death as a presentation of isolated non-compaction cardiomyopathy.

Left ventricular non-compaction cardiomyopathy (LVNC) is a rare disorder characterized by a thick myocardial wall with two distinct layers consisting of compacted and noncompacted myocardium. The major clinical manifestations of LVNC have been described as heart failure, cardiac arrhythmias, and cardioembolic events. In this report we present a case of a young woman with LVNC who presented with aborted sudden cardiac death. This is the second case of LVNC reported in Puerto Rico, but the first presenting with this complication. Recent advances in the field of cardiology allow the identification and diagnosis of this disease; thus, preventive and treatment strategies could be established for this potentially life-threatening condition. LVNC has to be considered in young patients presenting with sudden cardiac death.

Spontaneous hemothorax: first manifestation of pulmonary arteriovenous malformation in a patient with hereditary hemorrhagic telangiectasia.

Hereditary Hemorrhagio Telangiectasla (HHT) is a rare inherited autosomal dominant disorder characterized by systemic fibrovascular dysplasia making vessel walls more liable to spontaneous ruptures and injuries. Epistaxis is the first and the most common symptom; however patients may have a variety of serious complications due to vascular involvement of internal organs. In this report we present a case of a 39 year-old woman with recurrent epistaxis and family history of HHT who presented with right spontaneous hemothorax. Pulmonary angiography disclosed multiple pulmonary artery aneurysms with subsequent coil embolization. Considering that pulmonary arteriovenous malformations are associated with considerable morbidity and mortality, patients and family members with suspected HHT should be screened for these vascular malformations.

Ventricular tachycardia as a presentation of congenital left ventricular aneurysm.

Left ventricular aneurysm (LVA) describes a region of ventricular wall that is thinner than the adjacent myocardial segments, balloons outward and exhibits either akinesis or dyskinesis. Congenital LVA is diagnosed by exclusion with a very low incidence, especially in adult patients with very few cases reported. Clinically, most congenital LVA are asymptomatic. The most common complaints are typical angina or atypical chest pain followed by syncope and heart rhythm disturbances. We describe the case of a 26-year-old-woman that presented with monomorphic sustained ventricular tachycardia as a first manifestation of congenital LVA. Successful endoventricular circular patch placement, or Dor procedure was performed. Successful substrate modification for arrhythmia development was performed and confirmed by an electrophysiological study. This would constitute the first case of this nature reported in Puerto Rico.

[Chronic renal disease in Puerto Rico: incidence, prevalence, and mortality in 2000-2008]. / Enfermedad renal permanente en Puerto Rico: incidencia, prevalencia y mortalidad de 2000-2008.

BACKGROUND: End-Stage Renal Disease (ESRD) is a global public health problem. Although there are strategies for its prevention, the number of cases has increased. In order to understand current situation in Puerto Rico (PR) we review available data, which is presented in a descriptive report of the incidence, prevalence and mortality of ESRD during the period 2000-2008. In addition, we compare the incidence and prevalence rates with regard to other countries. METHODS: We used 2000-2008 USRDS statistics and the QIRN3 for patients on dialysis. Transplanted patients were excluded. Crude rates of incidence and prevalence in PR were calculated for comparison with the United States and other countries. Percentages were calculated to describe the demographic characteristics and primary diagnosis in 2008. RESULTS: During the period 2000-2008 the incidence rate increased by 21.6 percent; from 286.8 to 348.7 pmp. The prevalence rate increased by 27.3 percent; from 861.2 to 1096.2 pmp. The average annual growth in the incidence and prevalence was 2.4 percent and 3.0 percent respectively. During the same period, diabetes mellitus was the leading cause of ESRD reaching 67.4 percent of total new cases in 2008, while in the U.S. was 44.4 percent. Unadjusted mortality decreased slightly in 2008 to 18.5 percent. PR is the fifth country with the highest incidence of patient on dialysis and the first with ESRD due to diabetes mellitus. CONCLUSIONS: ESRD is becoming more common and prevalent in PR. We should be more aggressive in establishing public health strategies to reduce ESRD.

Population Kidney Health. A New Paradigm for Chronic Kidney Disease Management.

Statistical data extracted from national databases demonstrate a continuous growth in the incidence and prevalence of chronic kidney disease (CKD) and the ineffectiveness of current policies and strategies based on individual risk factors to reduce them, as well as their mortality and costs. Some innovative programs, telemedicine and government interest in the prevention of CKD did not facilitate timely access to care, continuing the increased demand for dialysis and transplants, high morbidity and long-term disability. In contrast, new forms of kidney disease of unknown etiology affected populations in developing countries and underrepresented minorities, who face socioeconomic and cultural disadvantages. With this background, our objective was to analyze in the existing literature the effects of social determinants in CKD, concluding that it is necessary to strengthen current kidney health strategies, designing in a transdisciplinary way, a model that considers demographic characteristics integrated into individual risk factors and risk factors population, incorporating the population health perspective in public health policies to improve results in kidney health care, since CKD continues to be an important and growing contributor to chronic diseases.

Drosophila vesicular monoamine transporter mutants can adapt to reduced or eliminated vesicular stores of dopamine and serotonin.

Physiologic and pathogenic changes in amine release induce dramatic behavioral changes, but the underlying cellular mechanisms remain unclear. To investigate these adaptive processes, we have characterized mutations in the Drosophila vesicular monoamine transporter (dVMAT), which is required for the vesicular storage of dopamine, serotonin, and octopamine. dVMAT mutant larvae show reduced locomotion and decreased electrical activity in motoneurons innervating the neuromuscular junction (NMJ) implicating central amines in the regulation of these activities. A parallel increase in evoked glutamate release by the motoneuron is consistent with a homeostatic adaptation at the NMJ. Despite the importance of aminergic signaling for regulating locomotion and other behaviors, adult dVMAT homozygous null mutants survive under conditions of low population density, thus allowing a phenotypic characterization of adult behavior. Homozygous mutant females are sterile and show defects in both egg retention and development; males also show reduced fertility. Homozygotes show an increased attraction to light but are mildly impaired in geotaxis and escape behaviors. In contrast, heterozygous mutants show an exaggerated escape response. Both hetero- and homozygous mutants demonstrate an altered behavioral response to cocaine. dVMAT mutants define potentially adaptive responses to reduced or eliminated aminergic signaling and will be useful to identify the underlying molecular mechanisms.

Systematic approach for the management of chronic kidney disease: moving beyond chronic kidney disease classification.

PURPOSE OF REVIEW: This review has two aims: to summarize the evolution of classification criteria for chronic kidney disease (CKD) for diagnosis, prognosis and forecasting population burden of illness; to move the discussion beyond classification to intervention by introducing an approach we describe as the 'Systematic Approach for the Management of CKD' (SAM-CKD). RECENT FINDINGS: There is now ample evidence against the use of estimated GFR (eGFR) as the sole criterion for classifying CKD for the purpose of diagnosis, risk stratification and prediction of progression. There is ample evidence that significant proteinuria is a powerful predictor of progression but even more so when combined with reduced eGFR for individual and population risk projection. Hypertension also is an important indicator in CKD progression but not in all studies. Beyond classification, there are no studies addressing standardization of management of CKD to achieve the outcomes articulated by any of the practice guidelines. SUMMARY: In this article we have moved the discussions of CKD beyond classification by introducing a clinical management tool, SAM-CKD, which couples a broader classification model with a systematic tool for management to foster standardization of CKD management for the future.