Fluorinated Carbohydrates as Lectin Ligands: Simultaneous Screening of a Monosaccharide Library and Chemical Mapping by 19F NMR Spectroscopy.

Molecular recognition of carbohydrates is a key step in essential biological processes. Carbohydrate receptors can distinguish monosaccharides even if they only differ in a single aspect of the orientation of the hydroxyl groups or harbor subtle chemical modifications. Hydroxyl-by-fluorine substitution has proven its merits for chemically mapping the importance of hydroxyl groups in carbohydrate-receptor interactions. 19F NMR spectroscopy could thus be adapted to allow contact mapping together with screening in compound mixtures. Using a library of fluorinated glucose (Glc), mannose (Man), and galactose (Gal) derived by systematically exchanging every hydroxyl group by a fluorine atom, we developed a strategy combining chemical mapping and 19F NMR T2 filtering-based screening. By testing this strategy on the proof-of-principle level with a library of 13 fluorinated monosaccharides to a set of three carbohydrate receptors of diverse origin, i.e. the human macrophage galactose-type lectin, a plant lectin, Pisum sativum agglutinin, and the bacterial Gal-/Glc-binding protein from Escherichia coli, it became possible to simultaneously define their monosaccharide selectivity and identify the essential hydroxyls for interaction.

Evaluating the Diagnostic Accuracy of a Portable, Motorized, and Remotely Controlled Slit Lamp Imaging Adaptor Prototype for Head-Mounted Displays.

Purpose: The purpose of this study was to validate the performance of a portable and remotely controlled slit lamp imaging adaptor. Methods: Twenty patients with anterior eye segment conditions participated in a randomized masked clinical trial. Imaging was performed using a Haag-Streit AG, BX 900 slit lamp biomicroscope and a new slit lamp prototype. Three ophthalmologists independently reviewed masked and randomized 2D images from both instruments and conducted physical eye examinations based on these images. Inter- and intra-grader reliability were assessed using kappa statistics, and sensitivity and specificity were determined with reference to the clinical eye examinations performed during the patients' visits. Results: The sensitivity and specificity of the evaluations with the prototype were 47.8% and 64.1%. Similarly, the evaluations from the conventional system obtained a sensitivity and specificity of 49.5% and 66.2%. The differences in the sensitivity and specificity between imaging modalities were not statistically significant (P > 0.05). The intra-grader reliability showed moderate to substantial agreement between the systems (κ = 0.522-0.708). The inter-grader reliability also indicated moderate agreement for the evaluations with the conventional system (κ = 0.552) and the prototype (κ = 0.474). Conclusions: This study presents a new prototype that exhibits diagnostic accuracy on par with conventional slit lamps and moderate reliability. Further studies with larger sample sizes are required to characterize the prototype's performance. However, its remote functionality and accessibility suggest the potential to extend eye care. Translational Relevance: The development of portable and remotely controlled eye imaging systems will enhance teleophthalmology services and broaden access to eye care at the primary care level.

Portable Anterior Eye Segment Imaging System for Teleophthalmology.

Objective: This study aims to compare a new prototype for a portable anterior eye segment imaging system with the standard method for ophthalmology examination. Methods: The new imaging system consisted of two IMX219 Arducam autofocus sensors (Arducam, China, Nanjing) for Raspberry Pi V2 camera module connected to a Raspberry Pi Zero W (Raspberry Pi Foundation, UK, Cambridge) that clips to a wearable headset. The 2D videos of the anterior eye segment were recorded with the new system and a 720p FaceTime HD camera (Apple, Cupertino, CA). Afterward, ophthalmologists evaluated the videos using a standard clinical eye examination form. These evaluations were compared with the standard slit-lamp clinical assessment performed during the patient's visit. Results: Thirty-five eyes were evaluated. The sensitivity and specificity percentages were statistically significant between the two imaging modalities (P ≤ 0.001). The evaluations performed from videos obtained with the new imaging system had better sensitivity and specificity percentages overall. However, statistically significant differences were only observed in cornea, anterior chamber, iris, and lens. Conclusions: Specificity percentages were higher than sensitivity percentages in both imaging modalities, indicating that video evaluations are less accurate for pathological screening. Nevertheless, the new system evaluations were significantly better than the webcam evaluations. Translational Relevance: This study presented an alternative system to assess eye conditions for telemedicine, one that provides more details than the current standard and uses new wearable headsets technologies.

Characterization of the immune response induced by a commercially available inactivated bluetongue virus serotype 1 vaccine in sheep.

The protective immune response generated by a commercial monovalent inactivated vaccine against bluetongue virus serotype 1 (BTV1) was studied. Five sheep were vaccinated, boost-vaccinated, and then challenged against BTV1 ALG/2006. RT-PCR did not detect viremia at any time during the experiment. Except a temperature increase observed after the initial and boost vaccinations, no clinical signs or lesions were observed. A specific and protective antibody response checked by ELISA was induced after vaccination and boost vaccination. This specific antibody response was associated with a significant increase in B lymphocytes confirmed by flow cytometry, while significant increases were not observed in T lymphocyte subpopulations (CD4(+), CD8(+), and WC1(+)), CD25(+) regulatory cells, or CD14(+) monocytes. After challenge with BTV1, the antibody response was much higher than during the boost vaccination period, and it was associated with a significant increase in B lymphocytes, CD14(+) monocytes, CD25(+) regulatory cells, and CD8(+) cytotoxic T lymphocytes.

Novel antimicrobial agents as alternative to chlorine with potential applications in the fruit and vegetable processing industry.

There has been an increasing demand for fresh fruit and vegetables in recent years. Along the processing line in fresh-cut vegetable production, disinfection is one of the most important processing steps affecting the quality and safety, and the shelf-life of the end produce. Although a range of antimicrobial compounds commonly termed biocides or disinfectants are available, chlorine has long been used to disinfect washing waters of fresh-cut vegetables. However, since chlorine reactions with organic matter lead to the production of by-products, alternative disinfectants to chlorine must be evaluated. A synthetic washing water formula has been developed to determine the antimicrobial efficiency of different families of potential disinfectants: quaternary ammonium compounds (QACs) as benzalkonium chloride (BZK), and didecyldimethylammonium chloride (DDAC); isothiazolinones (mixture of methylchloroisothiazolinone and methylisothiazolinone, CMIT:MIT 3:1 and 1:1); and essential oils (carvacrol, CAR). The twin configuration and higher length of the chains of alkyl groups of DDAC compared to BZK have led to a higher antimicrobial efficiency. In both cases, Gram-positive bacteria seemed to be much more sensitive to the QAC attack than Gram-negative. The opposite happened for CMIT:MIT. The chloro-substituted isothiazolinone (CMIT) has been proven to be much more effective than its unsubstituted form (MIT). In addition, in contrast to chlorine, its antimicrobial activity together with that of DDAC was not decreased when increasing the organic matter content of the water. Synergetic antimicrobial effects have been confirmed when combining BZK and CAR. MBC values were determined in SWW, during 90 s of contact time and Salmonella concentration of 103 CFU/mL, corresponding to: 100 (BZK), 30 (DDAC), 50 (CMIT:MIT 3:1), 100 (CMIT:MIT 1:1), 300 (CAR), 75 (BZK)-200 (CAR), and 9 (free chlorine) mg/L. MBC values for inactivating similar concentration of E. faecalis corresponded to: 50 (BZK), and 10 (DDAC) mg/L. Increasing contact times up to 5 min did not lead to higher antimicrobial efficiencies. CMIT:MIT 3:1 together with DDAC, and combinations of BZK-CAR seem to be a plausible alternative to chlorine.

Etiologic spectrum and functional outcome of the acute inflammatory myelitis.

Clinical, neuroimaging, and laboratory features are not specific enough to establish the etiological diagnosis of the acute inflammatory myelitis (AIM). Longitudinally extensive transverse myelitis (LETM) seen on magnetic resonance imaging (MRI) has been associated with a poor functional prognosis. The aim of this study was to assess the functional outcomes of a first AIM event comparing patients with LETM vs. no LETM on MRI and to report the differential diagnosis. Clinical, radiological, biochemical aspects were collected, and Winner-Hughes Functional Disability Scale (WHFDS) was performed after 3 and 6 months. Centromedullary lesions were associated with LETM, lateral lesions with partial lesion (PL), and brain MRI lesions with multiple sclerosis and acute encephalomyelitis disseminated. LETM patients were associated with a worse functional outcome as the need of a wheelchair after 3 and 6 months (OR = 7.61 p = 0.01; OR 4.8 p = 0.04, respectively), a walker or cane (OR = 11.0 p = 0.002, OR = 4.3 p = 0.03, respectively). In addition, we found a correlation between LETM and acute complete transverse myelitis and PL with acute partial transverse myelitis (83.3 and 90.9%, respectively; p < 0.0001). In conclusion, AIM is a heterogeneous syndrome from an etiological point of view and LETM patients had worse functional prognosis compared with PL after 3 and 6 months.

The use of infrared thermography as a non-invasive method for fever detection in sheep infected with bluetongue virus.

Fever, which is closely linked to viraemia, is considered to be both the main and the earliest clinical sign in sheep infected with bluetongue virus (BTV). The aim of this study was to evaluate the potential use of infrared thermography (IRT) for early detection of fever in sheep experimentally infected with bluetongue virus serotype 1 (BTV-1) and serotype 8 (BTV-8). This would reduce animal stress during experimental assays and assist in the development of a screening method for the identification of fever in animals suspected of being infected with BTV. Rectal and infrared eye temperatures were collected before and after BTV inoculation. The two temperature measures were positively correlated (r=0.504, P<0.05). The highest correlation between rectal and infrared temperatures was observed when temperatures were above physiological levels. IRT discriminated between febrile and non-febrile sheep with a sensitivity of 85% and specificity of 97%. The results showed that eye temperature measured using IRT was a useful non-invasive method for the assessment of fever in sheep infected with BTV under experimental conditions. Further research is required to evaluate the use of IRT under field conditions to identify potentially infected animals in bluetongue surveillance programmes.

Characterization of protection afforded by a bivalent virus-like particle vaccine against bluetongue virus serotypes 1 and 4 in sheep.

BACKGROUND: Bluetongue virus (BTV) is an economically important, arthropod borne, emerging pathogen in Europe, causing disease mainly in sheep and cattle. Routine vaccination for bluetongue would require the ability to distinguish between vaccinated and infected individuals (DIVA). Current vaccines are effective but are not DIVA. Virus-like particles (VLPs) are highly immunogenic structural mimics of virus particles, that only contain a subset of the proteins present in a natural infection. VLPs therefore offer the potential for the development of DIVA compatible bluetongue vaccines. METHODOLOGY/PRINCIPAL FINDINGS: Merino sheep were vaccinated with either monovalent BTV-1 VLPs or a bivalent mixture of BTV-1 VLPs and BTV-4 VLPs, and challenged with virulent BTV-1 or BTV-4. Animals were monitored for clinical signs, antibody responses, and viral RNA. 19/20 animals vaccinated with BTV-1 VLPs either alone or in combination with BTV-4 VLPs developed neutralizing antibodies to BTV-1, and group specific antibodies to BTV VP7. The one animal that showed no detectable neutralizing antibodies, or group specific antibodies, had detectable viral RNA following challenge but did not display any clinical signs on challenge with virulent BTV-1. In contrast, all control animals' demonstrated classical clinical signs for bluetongue on challenge with the same virus. Six animals were vaccinated with bivalent vaccine and challenged with virulent BTV-4, two of these animals had detectable viral levels of viral RNA, and one of these showed clinical signs consistent with BTV infection and died. CONCLUSIONS: There is good evidence that BTV-1 VLPs delivered as monovalent or bivalent immunogen protect from bluetongue disease on challenge with virulent BTV-1. However, it is possible that there is some interference in protective response for BTV-4 in the bivalent BTV-1 and BTV-4 VLP vaccine. This raises the question of whether all combinations of bivalent BTV vaccines are possible, or if immunodominance of particular serotypes could interfere with vaccine efficacy.

Detection of bluetongue serotype 4 in mouflons (Ovis aries musimon) from Spain.

Bluetongue serotype 4 (BTV4) has been detected for the first time in tissue samples from 2 mouflons (Ovis aries musimon) from the South of Spain, in a retrospective study. The samples included in this study had been fixed and paraffin-embedded for over a year prior to their analysis using a BTV group-specific and a BTV4-specific RT-PCR test. Lung and lymphatic nodes were found positive in both specimens. The amplified DNA was confirmed to be BTV4 by sequencing the RT-PCR products and comparing them with other sequences from GenBank. The combination of RNA extraction from paraffin-embedded samples and serotype-specific real-time RT-PCR assays provides the tools for the detection of BTV from samples stored for a long time. The results shown in this study set out the basis for a greater survey with fixed samples from different species of wild ruminants that the veterinary services have been collecting for years.

[Mechanisms of ureteral contraction-relaxation in nephritic colic]. / Mecanismos de contracción-relajación ureteral en el cólico nefrítico.

OBJECTIVE: From the clinical perspective, pharmacological research on ureteral dynamics--the contraction-relaxation mechanisms of the ureter--, has been prompted by renal colic. Studies of the events triggered by the calculus have been conducted to identify the pharmacological aspects that permit pain relief, passage of the calculus and protection of the kidney from injury caused by acute obstruction. METHODS: Many and varied studies on ureteral pharmacology, both in vivo and in vitro, have been carried out since the beginning of the 20th century. Numerous studies on the anatomical, neurophysiological and hormonal aspects, and different neuroactive substances have attempted to identify the behavior of the ureter under normal and pathological conditions. Since 1967, the Urology Department of the 'Jiménez Díaz' Foundation has investigated the mechanisms of ureteropelvic dynamics utilizing techniques developed at this institution, such as pyelomanometry, pressure/flow to constant pressure studies and antegrade pyelography. RESULTS: The different behavior of the ureter and the stimuli it receives according to the zone analyzed, are known. The classical neurohumoral mechanisms (adrenergic and cholinergic), ureteral pacemaker, effects of urinary pH and infection, action of glucagons, prostaglandins, as well as the new mechanisms of action mediated by substances and non-adrenergic non-cholinergic (NANC) receptors (tachykinins, nitric oxide (NO), vasoactive intestinal peptide (VIP), neuropeptide Y, etc.) have led to new concepts of ureteral contraction-relaxation. CONCLUSIONS: The current therapeutic strategy in renal colic utilizes non-steroidal antiinflammatory drugs (NSAID) and extracorporeal shock wave lithotripsy (ESWL) in situ for analgesia and resolution. Recent insight into ureteral dynamics attempt to promote the development of new drugs for enhanced and more effective management of renal colic.

Incidencia de aborto incompleto antes y después de instaurado un programa de procreación responsable / Incidence of incomplete abortion before and after established a responsible procreation program

Objetivo: Evaluar la posible disminución de abortos incompletos por efecto de un programa de Procreación Responsable (PR). Material y métodos: El diseño del estudio fue observacional descriptivo. Fue estudiada la incidencia del aborto incompleto durante veinte años consecutivos a través del índice L/P (número total de legrados por abortos incompletos/número total de partos anuales), y en dos períodos 1977-1986 (sin un programa PR) y 1987-1996 (con programa PR). Resultados: Observamos una significativa disminución del índice L/P en el decenio 1987-1996 respecto del decenio 1977-1986, (11,08 por ciento vs. 7,55 por ciento p <0,001), esta disminución mostró una tendencia exponencial sin estacionalidad (test de Mann-Whitney, p <0,001). El número de beneficiarias del programa de PR tuvo un crecimiento lineal de 337 en el primer año hasta 8.954 al final del decenio. En el decenio donde actuó el programa de PR, se observó que el índice L/P fue descendiendo de 10,0 por ciento hasta estabilizarse en un 7,5 por ciento a medida que se incrementaba el número de beneficiarias del programa. El riesgo de aborto para la población expuesta, atribuible a la no existencia del programa de PR fue de 34,6 por ciento [Odds ratio= 1,53 (I.C. 95 por ciento: 1,47-1,59)] y para la población general del 3,9 por ciento. Consideramos que el comportamiento del aborto provocado, estaría reflejado en la evolución del índice L/P analizado. Conclusión: El desarrollo de un programa de Procreación Responsable estuvo asociado con una disminución de la incidencia de aborto incompleto. (AU)

Factores de riesgo, patología asociada y características cervicales relacionadas con el éxito o fracaso de la uteroinhibición en la amenaza de parto pretérmino / Factors of risk, associated pathology and cervical characteristics related with the success or failure of the uteroinhibition in the preterm labor

El nacimiento pretérmino sigue siendo un problema perinatal importante. La infección amniótica con el consiguiente desencadenamiento de contracciones uterinas es la posibilidad más aceptada. En este estudio se analizan los factores de riesgo y características cervicales en pacientes con APP y su respuesta a la uteroinhibición. Las pacientes con edad menor a los 25 años tienen mayor riesgo de fracaso de la uteroinhibición. El peso promedio del RN fue menor en el grupo de uteroinhibición fallida, hallándose también en este grupo más RN con prematurez extrema. La patología más frecuentemente asociada fue la RPM. Las pacientes del grupo parto presentaron mayor dilatación cervical que las que prolongaron el embarazo (AU)

Factores de riesgo, patología asociada y características cervicales relacionadas con el éxito o fracaso de la uteroinhibición en la amenaza de parto pretérmino / Factors of risk, associated pathology and cervical characteristics related with the success or failure of the uteroinhibition in the preterm labor

El nacimiento pretérmino sigue siendo un problema perinatal importante. La infección amniótica con el consiguiente desencadenamiento de contracciones uterinas es la posibilidad más aceptada. En este estudio se analizan los factores de riesgo y características cervicales en pacientes con APP y su respuesta a la uteroinhibición. Las pacientes con edad menor a los 25 años tienen mayor riesgo de fracaso de la uteroinhibición. El peso promedio del RN fue menor en el grupo de uteroinhibición fallida, hallándose también en este grupo más RN con prematurez extrema. La patología más frecuentemente asociada fue la RPM. Las pacientes del grupo parto presentaron mayor dilatación cervical que las que prolongaron el embarazo

Incidencia de aborto incompleto antes y después de instaurado un programa de procreación responsable / Incidence of incomplete abortion before and after established a responsible procreation program

Objetivo: Evaluar la posible disminución de abortos incompletos por efecto de un programa de Procreación Responsable (PR). Material y métodos: El diseño del estudio fue observacional descriptivo. Fue estudiada la incidencia del aborto incompleto durante veinte años consecutivos a través del índice L/P (número total de legrados por abortos incompletos/número total de partos anuales), y en dos períodos 1977-1986 (sin un programa PR) y 1987-1996 (con programa PR). Resultados: Observamos una significativa disminución del índice L/P en el decenio 1987-1996 respecto del decenio 1977-1986, (11,08 por ciento vs. 7,55 por ciento p <0,001), esta disminución mostró una tendencia exponencial sin estacionalidad (test de Mann-Whitney, p <0,001). El número de beneficiarias del programa de PR tuvo un crecimiento lineal de 337 en el primer año hasta 8.954 al final del decenio. En el decenio donde actuó el programa de PR, se observó que el índice L/P fue descendiendo de 10,0 por ciento hasta estabilizarse en un 7,5 por ciento a medida que se incrementaba el número de beneficiarias del programa. El riesgo de aborto para la población expuesta, atribuible a la no existencia del programa de PR fue de 34,6 por ciento [Odds ratio= 1,53 (I.C. 95 por ciento: 1,47-1,59)] y para la población general del 3,9 por ciento. Consideramos que el comportamiento del aborto provocado, estaría reflejado en la evolución del índice L/P analizado. Conclusión: El desarrollo de un programa de Procreación Responsable estuvo asociado con una disminución de la incidencia de aborto incompleto.

Mecanismos de contracción-relajación ureteral en el cólico nefrítico / Uretral contraction-relaxation mechanisms in renal colic

Objetivos: La investigación farmacológica de la dinámica ureteral, de los mecanismos de contracción-relajación del uréter, ha sido motivada desde el punto de vista clínico por el cólico renal. Del estudio de los fenómenos que desencadena el impacto litiásico se pretende conocer aquellos aspectos farmacológicos que pudieran controlar el dolor, favoreciendo la expulsión del cálculo y proteger al riñón de los daños motivados por la obstrucción aguda. Métodos: Desde comienzos del s.XX son múltiples y muy variados los estudios realizados tanto in vitro como in vivo en investigación farmacológica ureteral. Numerosos estudios anatómicos, neurofisiológicos, hormonales, y de diversas sustancias neuroactivas han pretendido identificar el comportamiento del uréter en condiciones fisiológicas y patológicas. Desde 1967 en el Servicio de Urología de la Fundación "Jiménez Díaz" (1), se viene investigando en los mecanismos de la dinámica pieloureteral mediante técnicas desarrolladas en esta institución como son la pielomanometría, procedimientos de presión/flujo a presión constante y la pielografía anterógrada. Resultados: Se conoce el diferente comportamiento del uréter según la zona estudiada, y de los estímulos que reciba. Los mecanismos clásicos neurohumorales (adrenérgicos y colinérgicos), el pace-maker ureteral, el efecto del pH urinario y la infección, la acción del glucagón, las prostaglandinas, así como nuevos mecanismos de acción donde participan sustancias y receptores NANC (No Adrenérgicos No Colinérgicos) (taquicininas, óxido nítrico (NO), péptido intestinal vasoactivo (VIP), Neuropéptido Y,...), han introducido nuevos conceptos en cuanto a la contracción y relajación ureteral. Conclusiones: La estrategia terapéutica actual en el cólico renal comienza con la farmacología protagonizada por antiinflamatorios no esteroideos (AINEs) y la Litotricia Extracorpórea por Ondas de Choque (LEOC) realizada in situ con fines analgésicos y resolutivos. Los más novedosos descubrimientos en la dinámica ureteral pretenden incentivar el desarrollo de nuevos fármacos que controlen de la manera más idónea y eficaz el cólico renal (AU)

Colestasis gravídica: asociación entre la elevación de billirrubina total y peso al nacer mensor que 2.500 gramos / Cholestasis in pregnancy: association among the total bilirubin elevation and birth weight under 2500 grams

La colestais intrahepática del embarazo (CG) es la segunda causa de ictericia durante la gestación, luego de la hepatitis viral. Presenta una prevalencia variable según área geográfica y se la relaciona con potencial morbimortalidad perinatal y materna. En diversas revisiones realizadas por nuestro grupo en el Servicio de Obstetricia del Hospital Materno Infantil Ramón Sardá, hemos observado un claro rol diagnóstico para el valor de fosfatasa alcalina, pero a su vez esta enzima no aumenta su valor en asociación con complicaciones perinatales. Como contrapartida, en una revisión durante 1995 pareció observarse una relación entre complicaciones perinatales e incremento en los valores de bilirrubina total. Estas obvservaciones sugieren que la fosfatasa alcalina retiene un clave rol diagnþostico para CG, pero se insinúa una asociación entre complicaciones perinatales y elevación de los valores de bilirrubina total

Colestasis gravídica: asociación entre la elevación de billirrubina total y peso al nacer mensor que 2.500 gramos / Cholestasis in pregnancy: association among the total bilirubin elevation and birth weight under 2500 grams

La colestais intrahepática del embarazo (CG) es la segunda causa de ictericia durante la gestación, luego de la hepatitis viral. Presenta una prevalencia variable según área geográfica y se la relaciona con potencial morbimortalidad perinatal y materna. En diversas revisiones realizadas por nuestro grupo en el Servicio de Obstetricia del Hospital Materno Infantil Ramón Sardá, hemos observado un claro rol diagnóstico para el valor de fosfatasa alcalina, pero a su vez esta enzima no aumenta su valor en asociación con complicaciones perinatales. Como contrapartida, en una revisión durante 1995 pareció observarse una relación entre complicaciones perinatales e incremento en los valores de bilirrubina total. Estas obvservaciones sugieren que la fosfatasa alcalina retiene un clave rol diagnçostico para CG, pero se insinúa una asociación entre complicaciones perinatales y elevación de los valores de bilirrubina total