Pre-targeting of polymeric nanomaterials to balance tumour accumulation and clearance.

Pre-targeting of bispecific antibodies is probed to enhance tumour retention while limiting clearance of administered multifunctional branched PEGylated nanomedicines. The temporal influence of pre-targeting on polymer interaction with tumour cells and tissue is explored using in vitro assays through to preclinical validation.

The potential impact of post-COVID symptoms in the healthcare sector.

BACKGROUND: The phenomenon of post-COVID syndrome (PCS) is evolving from an abstract array of non-specific symptoms to an identifiable clinical entity of variable severity. Its frequency and persistence have implications for service delivery and workforce planning. AIMS: This study was aimed to assess the prevalence of symptoms consistent with PCS and the subjective degree of recovery in a cohort of healthcare workers, focusing on those who have returned to work. METHODS: A study population of 1176 was surveyed when attending for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody testing. Two sub-groups were identified: those with known (i.e. diagnosed on PCR testing) and assumed (i.e. antibody evidence of previous infection) SARs-CoV-2 infection, at least 12 weeks prior to the study. Each group was asked about their subjective degree of recovery and the nature of their persistent symptoms. Results were analysed via excel and SPSS. RESULTS: In total, 144 employees showed PCR evidence of previous infection, with 139 of these being infected at least 12 weeks prior to the study. Of these 139, only 19% (n = 26) reported feeling 100% recovered, and 71% reported persistent symptoms. Of those with assumed SARS-CoV-2 infection (n = 78), 32 (41%) were truly asymptomatic since the commencement of the pandemic, while 46 (59%) described symptoms suggestive of possible infection at least 12 weeks prior to the study. Of this latter group, 23% (n = 18) also reported residual symptoms. CONCLUSIONS: PCS is prevalent among this group, including those not previously diagnosed with COVID-19. Its' frequency and duration present challenges to employers with regards to the management of work availability and performance.

Ultra-short antibiotic prophylaxis guided by preoperative microbiological nasal swabs in endoscopic endonasal skull base surgery.

PURPOSE: Endoscopic endonasal skull base surgery (EESBS) is a clean-contaminated procedure. Guidelines regarding the antibiotic prophylaxis in EESBS have not been developed yet, and today, there are no universally accepted protocols. In this article, we investigated the efficacy of our new ultra-short antibiotic prophylaxis protocol for EESBS guided by the cultural results of preoperative microbiological nasal swabs. METHODS: We defined as "nasal swab-related antibiotic protocol" the administration of a first-generation cephalosporin (cefazolin 2 g) in patients whose nasal swabs revealed the presence of normal nasal flora or methicillin-sensitive Staphylococcus aureus (MSSA), and the administration of vancomycin 1 g intravenously in patients whose nasal swabs revealed the presence of methicillin-resistant Staphylococcus aureus (MRSA) or with reported cephalosporin/penicillin allergy. This case-control study included 120 patients who underwent EESBS. The case group included 60 cases who received the "nasal swab-related antibiotic protocol," while the control group included 60 cases who received the "standard hospital antibiotic protocol" used in neurosurgery (cefazolin 2 g plus metronidazole 500 mg at induction, and 2 g of cefazolin repeated after 180 min). RESULTS: The preoperative microbiological nasal swabs showed normal nasal flora in 42 patients (70%), MSSA in 17 patients (28.3%), and MRSA in 1 patient (1.6%). During the study period, no cases of meningitis or sinusitis occurred in the case group ("nasal swab-related antibiotic protocol"), while two infections (3.3%, 1 sinusitis and 1 meningitis) were reported in the control group ("standard hospital antibiotic protocol"). Mean length of hospitalization was 6.5 days for the case group and 8.5 days in the control group. "Standard hospital antibiotic protocol" is less expensive (range, 2.88-5.42 euros) compared with our new "nasal swab-related antibiotic protocol" (range, 10.02-32.56 euros), but in line with other antibiotic prophylaxis protocols reported in literature. DISCUSSION: The low complication rates of our case series (0%) is comparable to complication rates reported in literature (1.6% for meningitis and 8% for sinusitis). Compared with other perioperative antibiotic regimens reported in literature, the "nasal swab-related antibiotic protocol" is cheap and at least equally effective. We discuss the rationale on which we based the choice of chemoprophylaxis, the timing, and the length of our regimen. CONCLUSIONS: Our study confirmed the safety and efficacy of our easily applicable and low-cost antibiotic prophylaxis protocol.

Effect of different olive oil-derived antioxidants (hydroxytyrosol and 3,4-dihydroxyphenylglycol) on the quality of frozen-thawed ram sperm.

The aim of the present study was to evaluate the effect of the addition of different concentrations of two olive oil-derived antioxidants, hydroxytyrosol (3,4-dihydroxyphenylethanol, HT) and 3,4-dihydroxyphenylglycol (DHPG), on ovine semen during the freezing-thawing process. Sperm was collected, pooled and diluted with commercial extenders and then divided into aliquots supplemented with different concentrations (10 µg/ml, 30 µg/ml, 50 µg/ml and 70 µg/ml) of HT, DHPG and a mixture (MIX) of both antioxidants. A control group, without antioxidant, was also prepared. Sperm motility, viability, acrosome integrity, mitochondrial membrane potential and lipid peroxidation (LPO) were assessed. The results showed that frozen-thawed ram spermatozoa exhibited lower values for motility, membrane integrity, acrosome and mitochondrial membrane potential than fresh samples (P ≤ 0.01). However, when antioxidants were added, thawed spermatozoa exhibited relatively low LPO, recording values similar to fresh spermatozoa; by contrast, the control group of frozen-thawed spermatozoa without antioxidants exhibited significantly higher LPO (P ≤ 0.01). The addition of a HT+DHPG mixture (MIX) had a negative impact on sperm membrane and acrosome integrity, suggesting that a pure antioxidant supplementation has the potential to offer superior results. In conclusion, HT and DHPG exhibited a positive effect on the frozen-thawed spermatozoa inasmuch as they reduced the LPO. These olive oil-derived antioxidants have the potential to improve frozen-thawed sperm quality, although further studies should be carried out to analyse the antioxidant effect at different times after thawing.

Bereavement, multimorbidity and mortality: a population-based study using bereavement as an indicator of mental stress.

BACKGROUND: Mental stress is associated with higher mortality, but it remains controversial whether the association is causal or a consequence of a higher physical disease burden in those with a high mental stress load. Understanding causality is important when developing targeted interventions. We aimed to estimate the effect of mental stress on mortality by performing a 'natural' experiment using spousal bereavement as a disease-independent mental stressor. METHODS: We followed a population-based matched cohort, including all individuals in Denmark bereaved in 1997-2014, for 17 years. Prospectively recorded register data were obtained for civil and vital status, 39 mental and physical diagnoses, and socioeconomic factors. RESULTS: In total, 389 316 bereaved individuals were identified and 137 247 died during follow-up. Bereaved individuals had higher all-cause mortality than non-bereaved references in the entire study period. The relative mortality in the bereaved individuals was highest shortly after the loss (adjusted hazard ratio (aHR), first month: 2.50, 95% confidence interval (CI) 2.37-2.63; aHR, 6-12 months: 1.38, 95% CI 1.34-1.42). The excess mortality rate associated with bereavement rose with increasing number of physical diseases (1.33 v. 7.00 excess death per 1000 person-months for individuals with 0 v. ⩾3 physical conditions during the first month) and was exacerbated by the presence of mental illness. The excess mortality among bereaved individuals was primarily due to death from natural causes. CONCLUSIONS: Bereavement was associated with increased short-term and long-term mortality, even after adjustment for morbidities, which suggests that mental stress may play a causal role in excess mortality.

Treatment of Clostridium difficile infection: a national survey of clinician recommendations and the use of faecal microbiota transplantation.

Adherence to Clostridium difficile infection treatment guidelines is associated with lower recurrence rates and mortality as well as cost savings. This survey of Irish clinicians indicates that patients are managed using a variety of approaches. Faecal microbiota transplantation is potentially underused despite its recommendation in national and European guidelines.

Enantioselective capillary electrophoresis-mass spectrometry of amino acids in cerebrospinal fluid using a chiral derivatizing agent and volatile surfactant.

The sensitivity of coupled enantioselective capillary electrophoresis-mass spectrometry (CE-MS) of amino acids (AAs) is often hampered by the chiral selectors in the background electrolyte (BGE). A new method is presented in which the use of a chiral selector is circumvented by employing (+)-1-(9-fluorenyl)ethyl chloroformate (FLEC) as chiral AA derivatizing agent and ammonium perfluorooctanoate (APFO) as a volatile pseudostationary phase for separation of the formed diastereomers. Efficient AA derivatization with FLEC was completed within 10 min. Infusion experiments showed that the APFO concentration hardly affects the MS response of FLEC-AAs and presents significantly less ion suppression than equal concentrations of ammonium acetate. The effect of the pH and APFO concentration of the BGE and the capillary temperature were studied in order to achieve optimized enantioseparation. Optimization of CE-MS parameters, such as sheath-liquid composition and flow rate, ESI and MS settings was performed in order to prevent analyte fragmentation and achieve sensitive detection. Selective detection and quantification of 14 chiral proteinogenic AAs was achieved with chiral resolution between 1.2 and 8.6, and limits of detection ranging from 130 to 630 nM injected concentration. Aspartic acid and glutamic acid were detected, but not enantioseparated. The optimized method was applied to the analysis of chiral AAs in cerebrospinal fluid (CSF). Good linearity (R(2) > 0.99) and acceptable peak area and electrophoretic mobility repeatability (RSDs below 21% and 2.4%, respectively) were achieved for the chiral proteinogenic AAs, with sensitivity and chiral resolution mostly similar to obtained for standard solutions. Next to l-AAs, endogenous levels of d-serine and d-glutamine could be measured in CSF revealing enantiomeric ratios of 4.8%-8.0% and 0.34%-0.74%, respectively, and indicating the method's potential for the analysis of low concentrations of d-AAs in presence of abundant l-AAs.

Aldose reductase inhibitors and nanodelivery of diabetic therapeutics.

Nanotechnology is a rapidly emerging drug-delivery system that makes possible the controlled release of small molecules, and nanodelivery of therapeutic molecules using nanoparticles or nanogels represents a major improvement for more focused delivery of such therapeutic molecules. The delivery of insulin for the control of diabetes mellitus (DM) and aldose reductase inhibitor (ARI) for diabetic complications may provide better treatment of diabetes. A structural overview of aldose reductase including computational docking experiments with HAR-1, various ARIs, aldose-keto reductase, and nanodelivery of insulin, ARI's, and drug molecules are described.

An unusual case of Legionellosis.

Legionella species is a common cause of community-acquired pneumonia. However disease due to L. pneumophila serogroup 13 is rare and has not previously been reported in Ireland. It may not be detected by routine Legionella antigen and antibody kits. Due to these limitations, early culture should be considered when legionellosis is suspected. The potential therapeutic benefit of quinolones in the management of this disease is also illustrated.

Is there safety in numbers? The effect of cattle herding on biting risk from tsetse flies.

In sub-Saharan Africa, tsetse (Glossina spp.) transmit species of Trypanosoma which threaten 45-50 million cattle with trypanosomiasis. These livestock are subject to various herding practices which may affect biting rates on individual cattle and hence the probability of infection. In Zimbabwe, studies were made of the effect of herd size and composition on individual biting rates by capturing tsetse as they approached and departed from groups of one to 12 cattle. Flies were captured using a ring of electrocuting nets and bloodmeals were analysed using DNA markers to identify which individual cattle were bitten. Increasing the size of a herd from one to 12 adults increased the mean number of tsetse visiting the herd four-fold and the mean feeding probability from 54% to 71%; the increased probability with larger herds was probably a result of fewer flies per host, which, in turn, reduced the hosts' defensive behaviour. For adults and juveniles in groups of four to eight cattle, > 89% of bloodmeals were from the adults, even when these comprised just 13% of the herd. For groups comprising two oxen, four cows/heifers and two calves, a grouping that reflects the typical composition of communal herds in Zimbabwe, approximately 80% of bloodmeals were from the oxen. Simple models of entomological inoculation rates suggest that cattle herding practices may reduce individual trypanosomiasis risk by up to 90%. These results have several epidemiological and practical implications. First, the gregarious nature of hosts needs to be considered in estimating entomological inoculation rates. Secondly, heterogeneities in biting rates on different cattle may help to explain why disease prevalence is frequently lower in younger/smaller cattle. Thirdly, the cost and effectiveness of tsetse control using insecticide-treated cattle may be improved by treating older/larger hosts within a herd. In general, the patterns observed with tsetse appear to apply to other genera of cattle-feeding Diptera (Stomoxys, Anopheles, Tabanidae) and thus may be important for the development of strategies for controlling other diseases affecting livestock.

[Tics in children and adolescents: a retrospective analysis of 78 cases]. / Tics en niños y adolescentes: análisis retrospectivo de 78 casos.

INTRODUCTION: Tics are the most frequent abnormal movement in children. A familial history of tics and a personal and familial history of neurobehavioral disturbances are common in children with this abnormality. Tics may seriously compromise daily activities in affected individuals. OBJECTIVE: To identify the characteristics of tics in children and adolescents followed-up in the Neuropediatric Unit of the Hospital Geral de Santo António. MATERIALS AND METHODS: We performed a retrospective analysis of patients with tics based on information collected from medical records. The diagnostic criteria of the DSM IV-TR 2000 of the American Psychiatric Association were used. RESULTS: The medical records of 78 children were analyzed, 84.6 % of whom were boys. More than one third of the patients were aged 4 to 8 years old. In 5.1 % of the patients tics developed before the age of 2 years. A familial history of tics, depression and obsessive disorder traits was found in approximately 30 % of patients. The most frequent comorbidity was attention deficit hyperactivity disorder (67.9 %). The occurrence of pediatric autoimmune neuropsychiatric disorders associated with streptococcus infection (PANDAS) was suggested in five patients. In all patients, motor tics occurred before vocal tics. In more than two thirds of the patients, tics were simple. In 59.0 % of the patients, tics were chronic, and in 45.7 % of these met the criteria for Tourette's syndrome. A total of 43.1 % of the patients with chronic tics received pharmacotherapy, risperidone being the most frequently used drug. CONCLUSIONS: In general the results of the present study are in agreement with those of previous studies, underlining the need to consider a diagnosis of tics in young children and highlighting the importance of identification and appropriate treatment of comorbidities.

Tics en niños y adolescentes: análisis retrospectivo de 78 casos / Tics in children and adolescents: a retrospective analysis of 78 cases

Introducción Los tics son el trastorno del movimiento más frecuente en la edad pediátrica. Es común la existencia de historia familiar de tics y de antecedentes familiares y personales de trastornos neurocomportamentales. Los tics pueden comprometer de modo importante las actividades de la vida diaria del individuo. Objetivo Estudio de las características de los tics de niños y adolescentes de la Consulta de Neuropediatría del Hospital Geral de Santo António. Materiales y métodos Análisis retrospectivo de los casos de tics usando la información recogida de las respectivas historias clínicas. Se utilizaron los criterios del Manual diagnóstico y estadístico de los trastornos mentales en su cuarta revisión de textos (DSM-IV-TR) de 2000, de la Asociación Americana de Psiquiatría. Resultados Fueron analizadas las historias clínicas de 78 individuos, 84,6 % de los cuales eran del sexo masculino. Más de un tercio de los casos pertenecía al grupo etario de los 4 a los 8 años de edad. En el 5,1 % los tics se iniciaron antes de los 2 años. Historia familiar de tics, depresión y trazos de enfermedad obsesivo-compulsiva ocurrieron en aproximadamente un 30 % de los casos. La comorbilidad más frecuente fue el trastorno por déficit de atención e hiperactividad (TDAH) (67,9 %). Se verificó la posible ocurrencia de trastorno neuropsiquiátrico autoinmune pediátrico (PANDAS) en 5 casos. Los tics motores precedieron a los vocales en todos los casos. En más de dos tercios los tics eran simples. En el 59,0 % de los casos los tics eran crónicos, y el 45,7 % de éstos cumplían criterios de trastorno de Gilles de la Tourette. El 43,1 % de los individuos con tics crónicos habían sido medicados, la mayoría con risperidona. Conclusiones De un modo general los resultados de este estudio son concordantes con los descritos en la literatura especializada, subrayándose la necesidad de considerar el diagnóstico en edades precoces, y señalándose la importancia de identificación y terapéutica adecuada de las comorbilidades

Introduction Tics are the most frequent abnormal movement in children. A familial history of tics and a personal and familial history of neurobehavioral disturbances are common in children with this abnormality. Tics may seriously compromise daily activities in affected individuals. Objective To identify the characteristics of tics in children and adolescents followed-up in the Neuropediatric Unit of the Hospital Geral de Santo António. Materials and methods We performed a retrospective analysis of patients with tics based on information collected from medical records. The diagnostic criteria of the DSM IV-TR 2000 of the American Psychiatric Association were used. Results The medical records of 78 children were analyzed, 84.6 % of whom were boys. More than one third of the patients were aged 4 to 8 years old. In 5.1 % of the patients tics developed before the age of 2 years. A familial history of tics, depression and obsessive disorder traits was found in approximately 30 % of patients. The most frequent comorbidity was attention deficit hyperactivity disorder (67.9 %). The occurrence of pediatric autoimmune neuropsychiatric disorders associated with streptococcus infection (PANDAS) was suggested in five patients. In all patients, motor tics occurred before vocal tics. In more than two thirds of the patients, tics were simple. In 59.0 % of the patients, tics were chronic, and in 45.7 % of these met the criteria for Tourette's syndrome. A total of 43.1 % of the patients with chronic tics received pharmacotherapy, risperidone being the most frequently used drug. Conclusions In general the results of the present study are in agreement with those of previous studies, underlining the need to consider a diagnosis of tics in young children and highlighting the importance of identification and appropriate treatment of comorbidities

[Prenatal diagnosis and follow-up of congenital splenic cysts]. / Diagnóstico prenatal y seguimiento del quiste esplénico.

Congenital splenic cysts are uncommon entities, especially in children. Few cases diagnosed in the prenatal period have been reported in the literature. We describe two cases that were identified by prenatal sonography at 34 and 30 gestational weeks. Their follow-up until spontaneous full regression at 5 months and 2 years, respectively, is discussed. The etiology, clinical findings, and clinical course of this entity are reviewed.

Diagnóstico prenatal y seguimiento del quiste esplénico / Prenatal diagnosis and follow-up of congenital splenic cysts

Los quistes esplénicos congénitos son entidades poco frecuentes, particularmente en la edad pediátrica. En la literatura especializada existen pocos casos publicados con diagnóstico durante el período prenatal. Los autores describen 2 casos clínicos, identificados por ecografía prenatal a las 34 y 30 semanas de gestación, y su evolución posnatal hasta su resolución espontánea a los 5 meses y a los 2 años de vida, respectivamente. Se revisa la etiología, clínica y evolución de esta patología

Congenital splenic cysts are uncommon entities, especially in children. Few cases diagnosed in the prenatal period have been reported in the literature. We describe two cases that were identified by prenatal sonography at 34 and 30 gestational weeks. Their follow-up until spontaneous full regression at 5 months and 2 years, respectively, is discussed. The etiology, clinical findings, and clinical course of this entity are reviewed

Reversal of a hallmark of brain ageing: lipofuscin accumulation.

The prospect of removing cellular deposits of lipofuscin is of considerable interest because they may contribute to age related functional decline and disease. Here, we use a decapod crustacean model to circumvent a number of problems inherent in previous studies on lipofuscin loss. We employ (a) validated lipofuscin quantification methods, (b) an in vivo context, (c) essentially natural environmental conditions and (d) a situation without accelerated production of residual material or (e) application of pharmacological compounds. We use a novel CNS biopsy technique that produces both an anti-ageing effect and also permits longitudinal sampling of individuals, thus (f) avoiding conventional purely cross-sectional population data that may suffer from selective mortality biases. We quantitatively demonstrate that lipofuscin, accrued through normal ageing, can be lost from neural tissue. The mechanism of loss probably involves exocytosis and possibly blood transport. If non-disruptive ways to accelerate lipofuscin removal can be found, our results suggest that therapeutic reversal of this most universal manifestation of cellular ageing may be possible.

Glutathione peroxidases of the potato cyst nematode Globodera Rostochiensis.

We report the cloning and characterisation of full-length DNAs complementary to RNA (cDNAs) encoding two glutathione peroxidases (GpXs) from a plant parasitic nematode, the potato cyst nematode (PCN) Globodera rostochiensis. One protein has a functional signal peptide that targets the protein for secretion from animal cells while the other is predicted to be intracellular. Both genes are expressed in all parasite stages tested. The mRNA encoding the intracellular GpX is present throughout the nematode second stage juvenile and is particularly abundant in metabolically active tissues including the genital primordia. The mRNA encoding the secreted GpX is restricted to the hypodermis, the outermost cellular layer of the nematode, a location from which it is likely to be secreted to the parasite surface. Biochemical studies confirmed the secreted protein as a functional GpX and showed that, like secreted GpXs of other parasitic nematodes, it does not metabolise hydrogen peroxide but has a preference for larger hydroperoxide substrates. The intracellular protein is likely to have a role in metabolism of active oxygen species derived from internal body metabolism while the secreted protein may protect the parasite from host defences. Other functional roles for this protein are discussed.