An intranasal live-attenuated SARS-CoV-2 vaccine limits virus transmission.

The development of effective SARS-CoV-2 vaccines has been essential to control COVID-19, but significant challenges remain. One problem is intramuscular administration, which does not induce robust mucosal immune responses in the upper airways-the primary site of infection and virus shedding. Here we compare the efficacy of a mucosal, replication-competent yet fully attenuated virus vaccine, sCPD9-ΔFCS, and the monovalent mRNA vaccine BNT162b2 in preventing transmission of SARS-CoV-2 variants B.1 and Omicron BA.5 in two scenarios. Firstly, we assessed the protective efficacy of the vaccines by exposing vaccinated male Syrian hamsters to infected counterparts. Secondly, we evaluated transmission of the challenge virus from vaccinated and subsequently challenged male hamsters to naïve contacts. Our findings demonstrate that the live-attenuated vaccine (LAV) sCPD9-ΔFCS significantly outperformed the mRNA vaccine in preventing virus transmission in both scenarios. Our results provide evidence for the advantages of locally administered LAVs over intramuscularly administered mRNA vaccines in preventing infection and reducing virus transmission.

A non-transmissible live attenuated SARS-CoV-2 vaccine.

Live attenuated vaccines (LAVs) administered via the mucosal route may offer better control of the COVID-19 pandemic than non-replicating vaccines injected intramuscularly. Conceptionally, LAVs have several advantages, including presentation of the entire antigenic repertoire of the virus, and the induction of strong mucosal immunity. Thus, immunity induced by LAV could offer superior protection against future surges of COVID-19 cases caused by emerging SARS-CoV-2 variants. However, LAVs carry the risk of unintentional transmission. To address this issue, we investigated whether transmission of a SARS-CoV-2 LAV candidate can be blocked by removing the furin cleavage site (FCS) from the spike protein. The level of protection and immunity induced by the attenuated virus with the intact FCS was virtually identical to the one induced by the attenuated virus lacking the FCS. Most importantly, removal of the FCS completely abolished horizontal transmission of vaccine virus between cohoused hamsters. Furthermore, the vaccine was safe in immunosuppressed animals and showed no tendency to recombine in vitro or in vivo with a SARS-CoV-2 field strain. These results indicate that removal of the FCS from SARS-CoV-2 LAV is a promising strategy to increase vaccine safety and prevent vaccine transmission without compromising vaccine efficacy.

Mucin-Inspired Single-Chain Polymer (MIP) Fibers as Potent SARS-CoV-2 Inhibitors.

Mucins are the key component of the defensive mucus barrier. They are extended fibers of very high molecular weight with diverse biological functions depending strongly on their specific structural parameters. Here, we present a mucin-inspired nanostructure, produced via a synthetic methodology to prepare methacrylate-based dendronized polysulfates (MIP-1) on a multi gram-scale with high molecular weight (MW=450 kDa) and thiol end-functionalized mucin-inspired polymer (MIP) via RAFT polymerization. Cryo-electron tomography (Cryo-ET) analysis of MIP-1 confirmed a mucin-mimetic wormlike single-chain fiber structure (length=144±59 nm) in aqueous solution. This biocompatible fiber showed promising activity against SARS-CoV-2 and its mutant strain, with a remarkable low half maximal (IC50 ) inhibitory concentration (IC50 =10.0 nM). Additionally, we investigate the impact of fiber length on SARS-CoV-2 inhibition by testing other functional polymers (MIPs) of varying fiber lengths.

Tailoring the Electron Trapping Effect of a Biocompatible Triboelectric Hydrogel by Graphene Oxide Incorporation towards Self-Powered Medical Electronics.

Triboelectric nanogenerators (TENGs) are associated with several drawbacks that limit their application in the biomedical field, including toxicity, thrombogenicity, and poor performance in the presence of fluids. By proposing the use of a hemo/biocompatible hydrogel, poly(2-hydroxyethyl methacrylate) (pHEMA), this study bypasses these barriers. In contact-separation mode, using polytetrafluoroethylene (PTFE) as a reference, pHEMA generates an output of 100.0 V, under an open circuit, 4.7 µA, and 0.68 W/m2 for an internal resistance of 10 MΩ. Our findings unveil that graphene oxide (GO) can be used to tune pHEMA's triboelectric properties in a concentration-dependent manner. At the lowest measured concentration (0.2% GO), the generated outputs increase to 194.5 V, 5.3 µA, and 1.28 W/m2 due to the observed increase in pHEMA's surface roughness, which expands the contact area. Triboelectric performance starts to decrease as GO concentration increases, plateauing at 11% volumetric, where the output is 51 V, 1.76 µA, and 0.17 W/m2 less than pHEMA's. Increases in internal resistance, from 14 ΩM to greater than 470 ΩM, ζ-potential, from -7.3 to -0.4 mV, and open-circuit characteristic charge decay periods, from 90 to 120 ms, are all observed in conjunction with this phenomenon, which points to GO function as an electron trapping site in pHEMA's matrix. All of the composites can charge a 10 µF capacitor in 200 s, producing a voltage between 0.25 and 3.5 V and allowing the operation of at least 20 LEDs. The triboelectric output was largely steady throughout the 3.33 h durability test. Voltage decreases by 38% due to contact-separation frequency, whereas current increases by 77%. In terms of pressure, it appears to have little effect on voltage but boosts current output by 42%. Finally, pHEMA and pHEMA/GO extracts were cytocompatible toward fibroblasts. According to these results, pHEMA has a significant potential to function as a biomaterial to create bio/hemocompatible TENGs and GO to precisely control its triboelectric outputs.

Live-attenuated vaccine sCPD9 elicits superior mucosal and systemic immunity to SARS-CoV-2 variants in hamsters.

Vaccines play a critical role in combating the COVID-19 pandemic. Future control of the pandemic requires improved vaccines with high efficacy against newly emerging SARS-CoV-2 variants and the ability to reduce virus transmission. Here we compare immune responses and preclinical efficacy of the mRNA vaccine BNT162b2, the adenovirus-vectored spike vaccine Ad2-spike and the live-attenuated virus vaccine candidate sCPD9 in Syrian hamsters, using both homogeneous and heterologous vaccination regimens. Comparative vaccine efficacy was assessed by employing readouts from virus titrations to single-cell RNA sequencing. Our results show that sCPD9 vaccination elicited the most robust immunity, including rapid viral clearance, reduced tissue damage, fast differentiation of pre-plasmablasts, strong systemic and mucosal humoral responses, and rapid recall of memory T cells from lung tissue after challenge with heterologous SARS-CoV-2. Overall, our results demonstrate that live-attenuated vaccines offer advantages over currently available COVID-19 vaccines.

Body temperature variation controls pre-mRNA processing and transcription of antiviral genes and SARS-CoV-2 replication.

Antiviral innate immunity represents the first defense against invading viruses and is key to control viral infections, including SARS-CoV-2. Body temperature is an omnipresent variable but was neglected when addressing host defense mechanisms and susceptibility to SARS-CoV-2 infection. Here, we show that increasing temperature in a 1.5°C window, between 36.5 and 38°C, strongly increases the expression of genes in two branches of antiviral immunity, nitric oxide production and type I interferon response. We show that alternative splicing coupled to nonsense-mediated decay decreases STAT2 expression in colder conditions and suggest that increased STAT2 expression at elevated temperature induces the expression of diverse antiviral genes and SARS-CoV-2 restriction factors. This cascade is activated in a remarkably narrow temperature range below febrile temperature, which reflects individual, circadian and age-dependent variation. We suggest that decreased body temperature with aging contributes to reduced expression of antiviral genes in older individuals. Using cell culture and in vivo models, we show that higher body temperature correlates with reduced SARS-CoV-2 replication, which may affect the different vulnerability of children versus seniors toward severe SARS-CoV-2 infection. Altogether, our data connect body temperature and pre-mRNA processing to provide new mechanistic insight into the regulation of antiviral innate immunity.

Cyanoflan: A cyanobacterial sulfated carbohydrate polymer with emulsifying properties.

The extracellular polysaccharides produced by cyanobacteria have distinctive characteristics that make them promising for applications ranging from bioremediation to biomedicine. In this study, a sulfated polysaccharide produced by a marine cyanobacterial strain and named cyanoflan was characterized in terms of morphology, chemical composition, and rheological and emulsifying properties. Cyanoflan has a 71 % carbohydrate content, with 11 % of sulfated residues, while the protein account for 4 % of dry weight. The glycosidic-substitution analysis revealed a highly branched complex chemical structure with a large number of sugar residues. The cyanoflan high molecular mass fractions (above 1 MDa) and entangled structure is consistent with its high apparent viscosity in aqueous solutions and high emulsifying activity. It showed to be a typical non-Newtonian fluid with pseudoplastic behavior. Altogether, these results confirm that cyanoflan is a versatile carbohydrate polymer that can be used in different biotechnological applications, such as emulsifying/thickening agent in food or cosmetic industries.

PlayStation PortableTM como tratamiento de la ambliopía en los niños / PlayStation PortableTM as treatment for children with amblyopia

Objetivo: Determinar la efectividad de la terapia visual con el uso del PlayStation PortableTM en la ambliopía. Método: Se incluyeron 40 pacientes de 5-10 años de edad con ambliopía estrábica, anisometrópica o ambas, aleatorizados en 4 grupos según el tipo de terapia a utilizar (10 pacientes por grupo): grupo 1, PlayStation PortableTM y lentes rojo-verde; grupo 2, PlayStation PortableTM y lentes con vidrio esmerilado en el ojo fijador (no ambliope); grupo 3, PlayStation PortableTM y parche oclusivo en el ojo fijador; grupo 4, parche oclusivo en el ojo fijador sin el PlayStation PortableTM. Todos los pacientes utilizaron su refracción. Las actividades de los grupos 1 al 3 incluyeron jugar videojuegos y ver películas 1-2 horas al día; el grupo 4 podía realizar cualquier actividad. Se valoró la agudeza visual mejor corregida semanalmente, hasta completar 3 meses de tratamiento. En el postratamiento se valoró la agudeza visual mejor corregida mensualmente durante 3 meses. Resultados: En total se estudiaron 40 pacientes, de los cuales el 60 por ciento fueron del sexo femenino, con un promedio de edad de 8,2 años, rango de 5-10 años. El tipo más frecuente de ambliopía fue la estrábica (55 por ciento), seguido de la anisometrópica (37,5 por ciento) y ambas (7,5 por ciento). En cuanto al ojo afectado, en el 62,5 por ciento fue el ojo izquierdo y en el 37,5 por ciento el ojo derecho. Conclusiones: En este estudio el grupo con mejores resultados fue el de filtro rojo-verde. Al suspender la terapia se observó un deterioro visual en los cuatro grupos, sin regresar a la basal. Se demuestra que el PlayStation PortableTM funciona como terapia en la ambliopía con una mejoría en la agudeza visual mejor corregida(AU)

Objective: Determine the effectiveness of visual therapy with PlayStation PortableTM for amblyopia. Methods: The study sample was composed of 40 patients aged 5-10 years with strabismic amblyopia, anisometropic amblyopia or both, randomized to 4 groups according to the therapy to be used (10 patients per group): Group 1: PlayStation PortableTM and red-green lenses; Group 2: PlayStation PortableTM and frosted glass lenses on the fixating (non-amblyopic) eye; Group 3: PlayStation PortableTM and occlusive patch on the fixating eye; Group 4: occlusive patch on the fixating eye without PlayStation PortableTM. All the patients used their refraction. The activities performed by Groups 1-3 included playing video games and watching movies 1-2 hours per day; Group 4 could perform any activity. Best corrected visual acuity was measured weekly until completing 3 months of treatment. In the post-treatment period best corrected visual acuity was measured monthly for 3 months. Results: A total 40 patients were studied, of whom 60 percent were female, with a mean age of 8.2 years, range of 5-10 years. Strabismic amblyopia was the most common type (55 percent), followed by anisometropic amblyopia (37,5 percent) and both (7.5 percent). The affected eye was the left eye in 62.5 percent and the right eye in 37.5 percent. Conclusions: It was found that PlayStation PortableTM is effective as therapy for amblyopia, improving best corrected visual acuity. The group with the best results was the red-green filter group. Upon suspension of the therapy, visual deterioration was observed in the 4 groups, without returning to baseline values(AU)

Eligibility Criteria and Genetic Testing Results from a High-Risk Cohort for Hereditary Breast and Ovarian Cancer Syndrome in Southeastern Ontario.

Germline mutations in breast and ovarian cancer are rare, with approximately 5% to 10% and 13% being hereditary in origin, respectively. In 2001, the Ontario Ministry of Health and Long Term Care, in an effort to contain costs, defined criteria to determine an individual's eligibility for BRCA genetic screening. We studied a cohort of individuals that have undergone genetic testing at Kingston General Hospital between 2001 and late 2013. We focused on determining whether the 13 risk criteria, defined by an expert working group for the Ontario Ministry of Health and Long Term Care, have performed according to expectations in this cohort. Our findings show that all of the criteria perform well by identifying carriers at the expected 10% rate defined by the guidelines. We demonstrate that loose application of the risk criteria does not further enrich for BRCA variant carriers. Our assessment of the established risk criteria that have been in use in Ontario for more than a decade, provide evidence for their effectiveness, and offer insights into how they may be expanded or improved.

Roles for miR-375 in Neuroendocrine Differentiation and Tumor Suppression via Notch Pathway Suppression in Merkel Cell Carcinoma.

Dysfunction of key miRNA pathways regulating basic cellular processes is a common driver of many cancers. However, the biological roles and/or clinical applications of such pathways in Merkel cell carcinoma (MCC), a rare but lethal cutaneous neuroendocrine (NE) malignancy, have yet to be determined. Previous work has established that miR-375 is highly expressed in MCC tumors, but its biological role in MCC remains unknown. Herein, we show that elevated miR-375 expression is a specific feature of well-differentiated MCC cell lines that express NE markers. In contrast, miR-375 is strikingly down-regulated in highly aggressive, undifferentiated MCC cell lines. Enforced miR-375 expression in these cells induced NE differentiation, and opposed cancer cell viability, migration, invasion, and survival, pointing to tumor-suppressive roles for miR-375. Mechanistically, miR-375-driven phenotypes were caused by the direct post-transcriptional repression of multiple Notch pathway proteins (Notch2 and RBPJ) linked to cancer and regulation of cell fate. Thus, we detail a novel molecular axis linking tumor-suppressive miR-375 and Notch with NE differentiation and cancer cell behavior in MCC. Our findings identify miR-375 as a putative regulator of NE differentiation, provide insight into the cell of origin of MCC, and suggest that miR-375 silencing may promote aggressive cancer cell behavior through Notch disinhibition.

Ridge Preservation Comparing a Nonresorbable PTFE Membrane to a Resorbable Collagen Membrane: A Clinical and Histologic Study in Humans.

PURPOSE: The primary aim of this randomized, controlled, blinded clinical trial was to compare the effect of a resorbable collagen membrane (CM group) versus a nonresorbable high-density polytetrafluoroethylene membrane (PTFE group) on the clinical and histologic outcomes of a ridge preservation procedure. MATERIALS AND METHODS: All 24 sites received an intrasocket cancellous allograft and a buccal overlay bovine derived xenograft. RESULTS: The change in horizontal crestal ridge width was -1.4 ± 1.2 mm for the CM group, whereas the PTFE group lost -2.2 ± 1.5 mm, which was not statistically significant between groups (P > 0.05). Vertical ridge height change was -1.2 ± 1.5 for the CM group, whereas the PTFE group lost -0.5 ± 1.6, which was not significantly different between groups (P > 0.05). The percent vital bone was similar and not significantly different between groups. Primary closure was not obtained and the exposed membrane portion over the socket opening healed with keratinized tissue. CONCLUSION: The choice of a resorbable versus a nonresorbable barrier membrane did not affect the clinical or the histologic outcome of ridge preservation treatment.

The ABC Protocol in the Esthetic Zone: A Comprehensive Surgical and Prosthetic Approach.

The purpose of this article is to present a surgical and restorative protocol for the replacement of missing teeth in the esthetic zone. The ABC protocol consists of digitally guided implantation, autogenous bone graft (A), followed by bovine bone xenograft (B) and connective tissue graft (C). Autogenous bone is placed in contact with the implant surface to induce osseointegration; bovine bone xenograft is then applied to augment the ridge dimension and provide long-term stability. Connective tissue is used to provide additional volume. The ABC biomaterial sequence offers favorable hard and soft tissue dimensions and immediate provisional restoration predictably leads to an esthetically pleasing definitive prosthesis.

Origen y trayecto anómalo de las arterias coronarias evaluadas por tomografía computarizada multidetector, Clínica Internacional, 2012-2014 / Origin and anomalous trajectory of the coronary arteries evaluated by multidetector computed tomography, International Clinic, 2012-2014

El objetivo de la presente investigación fue determinar la prevalencia del origen y trayecto anómalo de las arterias coronarias mediante la angiotomografía multidetector. Se aplicó una hoja de recolección de datos. El estudio fue descriptivo de corte transversal. Se tomó una muestra de 260, se encontró que el 75.4 por ciento de pacientes atendidos fueron de sexo masculino mientras que 24.6 por ciento de sexo femenino, asimismo la mayor frecuencia se registró en el rango de edad de 40-60 años 65 por ciento. Se encontró que 2.7 por ciento presentaron anomalías de origen, de estos el 1,5 por ciento y 1,2 por ciento provienen del seno coronario izquierdo y derecho respectivamente. El 15,4 por ciento presentan anomalías de trayecto distribuyéndose en anomalías de trayecto retroaórtico 1,2 por ciento y puentes intramiocárdicos 14.2 por ciento. De los 40 pacientes que presentan puentes intramiocárdicos, 34 están en la arteria DA, de ellos 2 (0,8 por ciento) están ubicados en el segmento proximal, 28 (10.8 por ciento) en el segmento medio y 4 (1,5 por ciento) en el segmento distal. Además se observó presencia de puentes intramiocárdicos en la arteria Circunfleja 0,8 por ciento y 3,5 por ciento en la arteria coronaria derecha. La dominancia derecha es de mayor incidencia 95.8 por ciento frente al 4.2 por ciento correspondiendo a la dominancia izquierda. Conclusión: La prevalencia de anomalías de origen es de 2,7 por ciento y 15,4 por ciento para las anomalías de trayecto, la dominancia derecha es de 95,8 por ciento mientras que la dominancia izquierda 4,2 por ciento.

The aim of this investigation was to determine the prevalence of origin and anomalous trajectory of the coronary arteries by multidetector CT angiography. A sheet of data collection was applied. The study was descriptive of cross section. A sample of 260 was taken, it was found that 75.4 per cent of patients treated were male while 24.6 per cent female, also the highest rate was recorded in the age range of 40-60 years 65 per cent. It was found that 2.7 per cent had anomalies of origin of these 1.5 per cent and 1.2 per cent come from the left and right coronary sinus respectively. 15.4 per cent have anormalities path anomalies distributed in retroaortic 1.2 per cent and 14.2 per cent intramyocardial bridges. Of the 40 patients with intramyocardial bridges 34 are in them LAD, 2 (0.8 per cent) are located in the proximal segment 28 (10.8 per cent) in the middle segment and 4 (1.5 per cent) in the distal segment. Besides the presence of intramyocardial bridges was observed in the circumflex artery 0.8 per cent and 3.5 per cent in the right coronary artery. Right dominance is most prevalent 95.8 per cent versus 4.2 per cent corresponding to the left dominance. Conclusion: The prevalence of anomalies of origin is 2.7 per cent and 15.4 per cent for abnormal trajectory, right dominance is 95.8 per cent, while 4.2 per cent left dominance.

Percepción de conflicto intergrupal y su relación con la adhesión a creencias esencialistas / Perception of the intergroup conflict and its correlation with adherence to essentialist beliefs

La presente investigación estudia cómo se vinculan la percepción de un conflicto entre dos grupos (endogrupo y exogrupo) y la adherencia a creencias esencialistas. La hipótesis de trabajo es que la percepción de un mayor nivel de conflicto entre el endogrupo y un exogrupo se asocia a un aumento en las creencias esencialistas, es decir, se vería incrementado al pensar que los grupos existen como consecuencia de elementos profundos compartidos por sus miembros, que los convierten en grupos reales y naturales (no creados socialmente). Esta hipótesis se enmarca en una nueva orientación respecto de la aplicación de esta teoría implícita, en el sentido de tratar de comprender -más que sus consecuencias negativas- los virtuales beneficios secundarios para el grupo que opera con ellas. En dos estudios similares (N1 = 180, N2 = 162), que utilizaron un muestreo no aleatorio intencional y un diseño no experimental transversal y correlacional, se midieron las variables "percepción de conflicto" y "creencias esencialistas respecto al propio grupo y a otro grupo". Los resultados van en la dirección de nuestras predicciones e indican que, efectivamente, ambas variables se encuentran vinculadas. Se discute en torno a la posible interpretación causal de estos resultados y sus limitaciones.

This research study covers the relation between perception of conflict (in two groups: intragroup and extragroup) and adherence to essentialist beliefs. The hypothesis made Social identity states that perception of a higher conflict level between intragroup and extragroup is associated with an increase in essentialist beliefs. This means that this increase occurs pursuant to the belief that groups exist as a consequence of sharing profound elements amongst members, thus becoming real and natural (not socially created) groups. This hypothesis establishes a new approach to the application of this implicit theory, as it seeks to understand not only its negative consequences, but also its potential ancillary benefits for the groups which operate under such negative consequences. The two variables were measured in two similar studies (N1=180, N2=169) which used non-random sampling and a non-experimental cross-correlational design.The variables used were "conflict perception" and "essentialist intragroup extragroup beliefs".The results are in line with our predictions, showing that both variables are related. A discussion is presented on potential causal interpretation of these results and their limitations.

Platelet-rich plasma-assisted guided bone regeneration for ridge augmentation: a randomized, controlled clinical trial.

BACKGROUND: Platelet-rich plasma (PRP) contains a number of biologically active growth factors, and previous studies have reported conflicting ridge augmentation results. The primary aim of this randomized, controlled, masked, clinical trial was to determine if PRP combined with a rapidly resorbing cancellous allograft would enhance the regenerative result compared with an allograft without PRP. METHODS: Thirty-two patients with an edentulous ridge defect were sequentially entered into the study; four were excluded from data analysis. Fourteen patients received a cancellous allograft (CAN group) and the other 14 received a cancellous allograft mixed with PRP (PRP group). All 28 grafted sites were covered with a resorbable polylactide membrane. After elevation of a full-thickness flap, horizontal ridge dimensions were measured with a digital caliper at the crest and 5 mm apical to the crest. Vertical ridge dimensions were measured from a tooth-supported stent. All sites were reentered at 4 months, and a trephine core was obtained for histologic analysis before implant placement. RESULTS: The crestal ridge width for the CAN group had a mean gain of 2.0 ± 1.2 mm, whereas the PRP group gained 2.9 ± 1.0, and the difference was statistically significant between groups (P <0.05). The percent vital bone was 36% ± 14% for the CAN group compared with 51% ± 15% for the PRP group and was statistically significant between groups (P <0.05). Loss of augmented ridge width was 34% ± 17% for the CAN group and 28% ± 17% for the PRP group (P >0.05). CONCLUSION: These clinical and histologic findings suggest that PRP enhanced bone regeneration and resulted in increased horizontal bone gain and percentage vital bone.

Ridge preservation comparing socket allograft alone to socket allograft plus facial overlay xenograft: a clinical and histologic study in humans.

BACKGROUND: Previous studies of ridge preservation showed a loss of ≈18% or 1.5 mm of crestal ridge width in spite of treatment. The primary aim of this randomized, controlled, masked clinical trial is to compare a socket graft to the same treatment plus a buccal overlay graft, both with a polylactide membrane, to determine if loss of ridge width can be prevented by use of an overlay graft. METHODS: Twelve patients who served as positive controls received an intrasocket mineralized cancellous allograft (socket group), and 12 patients received the same socket graft procedure plus buccal overlay cancellous xenograft (overlay group). Horizontal ridge dimensions were measured with a digital caliper, and vertical ridge changes were measured from a stent. Before implant placement, at 4 months, a trephine core was obtained for histologic analysis. RESULTS: The mean horizontal ridge width at the crest for the socket group decreased from 8.7 ± 1.0 to 7.1 ± 1.5 mm for a mean loss of 1.6 ± 0.8 mm (P <0.05), whereas the same measurement for the overlay group decreased from 8.4 ± 1.4 to 8.1 ± 1.4 mm for a mean loss of 0.3 ± 0.9 mm (P >0.05). The overlay group was significantly different from the socket group (P <0.05). Histologic analysis revealed that the socket group had 35% ± 16% vital bone, and the overlay group had 40% ± 16% (P >0.05). CONCLUSIONS: The overlay treatment significantly prevented loss of ridge width and preserved or augmented the buccal contour. The socket and overlay groups healed with a high percentage of vital bone.

Inhibition of nitric oxide synthesis for four days induces vascular abnormalities and myocardial infarct areas but not significant arterial hypertension / Inibição da síntese do óxido nítrico durante quatro dias induz anormalidades vasculares e áreas de infarto miocárdico, porém, não induz hipertensão arterial significativa

BACKGROUND: Nitric oxide is an endothelium vasorelaxing factor and at least in some cases is the main cause of arterial hypertension, which is one of the most important risk factors of cardiovascular diseases. In Brazil, cardiovascular diseases are the first cause of mortality, representing about 30% of the total deaths. The L-NAME (Nω-nitro-arginine-methyl-ester) blocks the nitric oxide synthesis necessary to maintain the normal arterial pressure. OBJECTIVE: To study lesions in myocardium due to the inhibition of nitric oxide synthesis during four days (via L-NAME oral administration, concentration: 75 mgs versus 100 mL-1). METHODS: Fourteen normotensive young adults Wistar rats were submitted, during four days, to L-NAME. Six rats were utilized as the Control Group. At day 4 of the experiment, the animals were anesthetized, weighed, and their thoraxes were opened, and the cardiotomy was performed. The hearts were weighed, fixed, and processed using routine methods, and they were sectioned in 3 µm and stained. RESULTS: Abnormalities were observed in the wall of arterial vessels of any dimension, as vascular damage with increasing wall thickness related mainly to proliferation of arterial smooth muscle cell in submitted animals. Proliferation of cells in the intimal layer and its thickening were also observed in small arterial vessels (arteriole). Infarct areas were present. CONCLUSIONS: The present data suggested that inhibition of nitric oxide synthesis for four days induces vascular abnormalities and myocardial infarct areas, but not arterial hypertension.

CONTEXTO: O óxido nítrico é um fator de relaxamento vascular e, pelo menos em certos casos, é a principal causa de hipertensão arterial no ser humano. A hipertensão arterial é um importante fator de risco de doenças cardiovasculares. No Brasil, as doenças cardiovasculares são a primeira causa de mortalidade, representando cerca de 30% do total de óbitos. O L-NAME (Nω-nitro-arginina-metil-éster, Sigma Chemical, St. Louis) bloqueia a síntese do óxido nítrico necessária para a manutenção da pressão arterial normal. OBJETIVO: Estudar as lesões miocárdicas ocorridas por razão da inibição da síntese do óxido nítrico durante quatro dias (por meio da administração oral de L-NAME em concentração de 75 mgs versus 100 mL-1). MÉTODOS:Quatorze ratos Wistar jovens normotensos adultos foram submetidos durante quatro dias ao L-NAME. Seis foram utilizados como Grupo Controle. Aos quatro dias de experimento, os animais foram anestesiados, pesados, os tórax foram abertos e a cardiomiotomia foi efetuada. Os corações foram pesados, fixados e processados usando métodos de rotina e cortados em 3 µm de espessura e corados. RESULTADOS: As anormalidades foram observadas nas paredes arteriais de vasos de todos os calibres, como, por exemplo, o aumento da parede arterial relacionada principalmente à proliferação das células musculares lisas dos animais submetidos ao bloqueio do óxido nítrico. Também foi identificada proliferação das células da túnica íntima e seu espessamento nos vasos arteriais de pequeno calibre (arteríolas). Áreas de infarto estavam presentes. CONCLUSÕES: Os resultados sugerem que a inibição do óxido nítrico durante quatro dias induz anormalidades vasculares e áreas de infarto do miocárdio, contudo, não induz hipertensão arterial.

Effect of surface chemistry on bacterial adhesion, viability, and morphology.

Helicobacter pylori (H. pylori) is one of the most common infectious agents in the world and it is thought to colonize the gastric mucosa of about half of the world's population causing several gastric diseases. In this work, the effect of surface chemistry on H. pylori nonspecific adhesion, viability, and morphology was evaluated using three H. pylori strains with different adhesins expression profile. Self-assembled monolayers (SAMs) of alkanethiols on gold were used to obtain surfaces exposing different functional groups: OH, CH3, and ethylene glycol (EG4). Bacterial adhesion onto the surfaces reached a plateau at 2 h. There was a correlation between adhesion and the exposed surface group, with bacterial cells adhering preferentially to CH3-SAMs while EG4-SAMs prevented H. pylori adhesion during the entire adhesion test (24 h). Surfaces that presented the EG4 group were also the only ones that significantly reduced the viability of adhered bacteria. Surface chemistry also influenced the morphology of adhered bacteria. The H. pylori rod shape observed in the control (Tissue Culture Polyethylene-TCPE) was only retrieved on CH3-SAMs. This work demonstrates that surface chemistry, namely specific functional groups on the material, influence the nonspecific adsorption of H. pylori. Moreover, the features of the bacterial strain and the surface chemistry can alter the adhesion kinetics, as well as the morphology and viability of attached bacteria.

Disector Z-axis mechanical method for stereology

The purpose of this work is to calibrate a not expensive microscope to be applied in Optical Disector estimation. The evaluation of "Z-axis" bias and the "Z-axis" calibration were made utilizing a cover slip and a "manual digimatic outside micrometer scale" (Mitutoyo, Japan). Calibrating the cover slip we performed the calibration of the "Z-axis" of a microscope. In the cover slip two lines were painted with different colors using a pen glass. A blue line was painted on the up surface and another line (red) on the bottom surface of the cover slip forming a cross. Two metal rings with one palette welded in each were adapted in the microscope. Other palette was welded in the gross focuses in order to restrict the route of the fine focuses (Z-axis study) using the two palettes fixed in both rings. Results show that 10 micrometers in "Z-axis" were equal to 3.2 micrometers in the scale of its fine focuses of the microscope. Then, a Disector of 10μm (10μm in Z-axis) is equal to 3.2 micrometers in the fine focuses of this microscope. In conclusion, "Z-axis" calibration is crucial to assure enough precision for Disector Method since the equipment can be manufactured without the ideal precision or its precision can be lost after use.

O propósito deste trabalho é a Calibração de um microscópio comum de baixo custo de forma a usá-lo para estimativas do Método Disector Óptico. A avaliação do viés e a calibração do "eixo-Z" foram feitas usando uma lamínula e um "micrômetro manual digital" (Mitutoyo, Japan). Com a cali-bração da lamínula, calibramos o "eixo-Z" de um microscópio. Foram pintadas duas linhas com diferentes cores utilizando canetas para vidro. Uma linha (azul) foi pintada na superfície superior da lamínula e outra linha (vermelha) foi pintada na superfície inferior da lamínula, formando uma cruz. Dois anéis de metal com uma paleta de metal soldada a cada um deles foram adaptados ao micrométrico do microscópio. Outra paleta foi soldada ao macrométrico do mesmo microscópio, o que foi feito de forma a limitar o percurso do micrométrico (eixo-Z) pela ação desta em conjunto com a ação das duas paletas fixadas no micrométrico. Os resultados mostraram que 10 micrômetros no "eixo-Z" do microscópio foi igual a 3,2 na escala do seu micrométrico. Assim, um Disector de 10μm (10μm no eixo-Z) é igual a 3,2 micrômetros no micrométrico do microscópio utilizado. Concluindo, a calibração do eixo-Z é crucial para assegurar a precisão suficiente para as avaliações usando o Método Disector, já que os equipamentos podem ser manufaturados sem a precisão ideal ou podem perder sua precisão durante o tempo com o uso.

Success rate of immediate implants placed and restored by novice operators.

AIMS: The primary aim of this study was to evaluate the 1-year crestal bone loss and success rate of an immediately placed single-stage implant placed and restored by novice operators. A secondary aim was to determine the patient's assessment of the appearance of the final restoration. METHODS: Fifty-one patients received a tooth extraction and placement of at least 1 immediate implant by a Graduate Periodontics resident. Clinical and radiographic measurements were taken at the surgical, 4-month, and 1-year follow-up visits. After at least 3 months healing, dental students restored the implants with either a crown or an overdenture. Patient satisfaction was assessed using 5 categories: excellent, very good, good, fair, or poor. RESULTS: Sixty-two immediate implants were placed. The success rate was 100% at the 12-month visit and was subclassified as grade 3 because of the mean first year bone loss of 1.3 +/- 1.0 mm. Using the 2008 classification of Misch et al, 42 implants were classified as success optimum health, 19 as survival satisfactory health, and 1 as survival compromised health. Radiographic bone loss was stratified by implant platform position relative to the alveolar crest and changed from time 0 to time 12 by -1.0 +/- 1.2 mm for the supracrestal group (n = 25, P < 0.05), -1.5 +/- 0.9 mm for the crestal group (n = 31, P < 0.05), and -1.3 +/- 1.2 mm for the subcrestal group (n = 6, P < 0.05). The supracrestal group had significantly less bone loss than either the crestal or the subcrestal group (P < 0.05). The appearance of the final restoration at 1 year was rated excellent by 82% of patients, very good by 16%, and good by 2%. CONCLUSIONS: Immediate implant placement by novice operators using routine dental school procedures was a highly predictable procedure as indicated by the 100% success rate at 12 months. Most patients rated the restoration appearance as excellent.