Anatomy and academies of art II - a tale of two cities.

Anatomy played a significant role in the establishment of academies in art, initially in Italy and France, and then more widely in Europe and the Americas. This paper considers the role of anatomy in two such academies, the Royal Academy of Arts in London, and the Royal Hibernian Academy of Arts in Dublin. In both cases, anatomy teaching for art students was formalised by the appointment of a Professor of Anatomy, positions that continue to this day. The first Professor of Anatomy in the RA, William Hunter, set the standard by delivering lectures, carrying out dissections and producing écorchés. Some of his successors have published anatomy books specifically for artists, but their enthusiasm has varied. Unlike the continuity of the RA, the RHA has only had bespoke premises from 1826 to 1916, and from 1985 onwards, and its Schools or School have operated from 1826 to 1942, and from 2008 onwards. Anatomy teaching was a casualty of the decline of the formal art academy in the 20th century, but the fortunes of both are reviving in the early 21st century.

Anatomy and academies of art I: founding academies of art.

The structure of the human body and its parts is of obvious relevance in medicine, but it has also played a role in art. Accurate observation of surface or external anatomy is essential in both disciplines, and its understanding has been enhanced by knowledge of what is found beneath the skin, the internal anatomy, usually based on dissection. The role of anatomy in art in general, and in academies of art in particular, is the theme of this paper. The revival of dissection in 14th-century Italy was, if not causative, at least coincidental with the Renaissance. In 1563, Vasari founded the Accademia del Disegno in Florence, with una Anatomia included in its regulations. As a liberal art taught by university graduates, anatomy helped raise the status of painters and sculptors from artisans to artists and from guild to academy. Anatomy teaching was required in subsequent academies in Rome (1593) and Paris (1648), where the pattern of drawing from drawings, from casts, and from life was established and a Professor of Anatomy appointed in 1777. Anatomy was central to two of the Academy's most important genres, history painting and portraiture. The Academy system, with its emphasis on anatomy, spread to other European cities and to the Caribbean and the Americas from the 17th to the 19th centuries. This paper is concerned with the role of anatomy in the founding of art academies in general, while its companion paper, 'A Tale of Two Cities', considers the cases of the academies in London and Dublin in particular.

Comparison of two fetoscopic open neural tube defect repair techniques: single- vs three-layer closure.

OBJECTIVES: We reported previously on an exteriorized-uterus fetoscopic repair for open neural tube defect (ONTD) using a single-layer closure (SLC) technique. However, because SLC was associated with a high rate of cerebrospinal fluid (CSF) leakage at birth, we developed a three-layer closure (3LC) technique comprising a bovine collagen patch, a myofascial layer and a skin layer. The aims of this study were to compare SLC and 3LC in terms of intraoperative, postoperative and obstetric outcomes, as well as short-term neonatal neurologic and non-neurologic outcomes. METHODS: This was a retrospective analysis of prospectively collected data, from 32 consecutive SLC controls and 18 consecutive 3LC cases, that underwent exteriorized-uterus two-port fetoscopic repair of ONTD at our center, between April 2014 and December 2018. All patients satisfied the Management of Myelomeningocele Study (MOMS) criteria. Obstetric, maternal, fetal and early neonatal outcomes were compared between the SLC and 3LC groups. RESULTS: Maternal demographics and mean gestational age (GA) at fetal surgery (25.0 ± 0.7 vs 25.0 ± 0.5 weeks' gestation; P = 0.96), and at delivery (36.5 ± 3.5 vs 37.6 ± 3.0 weeks; P = 0.14), were similar between the SLC and 3LC groups, respectively. The rate of preterm prelabor rupture of membranes (PPROM) < 37 weeks (28% vs 29%; P = 0.9), mean GA at PPROM (32.3 ± 3.4 vs 32.7 ± 1.9 weeks; P = 0.83) and rate of vaginal delivery (50% vs 47%; P = 0.84) were similar for the SLC vs 3LC groups, respectively. In pregnancies that had SLC compared with those that had 3LC, there was a significantly higher incidence of CSF leakage at birth (8/32 (25%) vs 0/17 (0%); P = 0.02) and a significantly lower rate of reversal of hindbrain herniation at 6 weeks postoperatively (18/30 (60%) vs 14/15 (93%); P = 0.02). The rate of infants that met the MOMS criteria for shunt placement or died before 12 months of age (23/31 (74%) vs 7/12 (58%); P = 0.31) and those that required treatment for hydrocephalus by 12 months (15/32 (47%) vs 4/12 (33%); P = 0.42) were similar between the SLC and 3LC groups, respectively. CONCLUSIONS: Compared to SLC, 3LC preserves the fetal and obstetric benefits of fetoscopic repair and shows improved rates of CSF leakage and reversal of hindbrain herniation at 6 weeks postoperatively. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Elective delivery at 34 weeks vs routine obstetric care in fetal gastroschisis: randomized controlled trial.

OBJECTIVE: To evaluate whether elective preterm delivery (ED) at 34 weeks is of postnatal benefit to infants with isolated gastroschisis compared with routine obstetric care (RC). METHODS: Between May 2013 and September 2015, all women with a sonographic diagnosis of fetal gastroschisis referred to a single tertiary center, before 34 weeks' gestation, were invited to participate in this study. Eligible patients were randomized to ED (induction of labor at 34 weeks) or RC (spontaneous labor or delivery by 37-38 weeks, based on standard obstetric indications). The primary outcome measure was length of time on total parenteral nutrition (TPN). Secondary outcomes were time to closure of gastroschisis and length of stay in hospital. Outcome variables were compared using appropriate statistical methods. Analysis was based on intention-to-treat. RESULTS: Twenty-five women were assessed for eligibility, of whom 21 (84%; 95% CI, 63.9-95.5%) agreed to participate in the study; of these, 10 were randomized to ED and 11 to RC. The trial was stopped at the first planned interim analysis due to patient safety concerns and for futility; thus, only 21 of the expected 86 patients (24.4%; 95% CI, 15.8-34.9%) were enrolled. Median gestational age at delivery was 34.3 (range, 34-36) weeks in the ED group and 36.7 (range, 27-38) weeks in the RC group. One patient in the ED group delivered at 36 weeks following unsuccessful induction at 34 weeks. Neonates of women who underwent ED, compared to those in the RC group, showed no difference in the median number of days on TPN (54 (range, 17-248) vs 21 (range, 9-465) days; P = 0.08), number of days to closure of gastroschisis (7 (range, 0-15) vs 5 (range, 0-8) days; P = 0.28) and length of stay in hospital (70.5 (range, 22-137) vs 31 (range, 19-186) days; P = 0.15). However, neonates in the ED group were significantly more likely to experience late-onset sepsis compared with those in the RC group (40% (95% CI, 12.2-73.8%) vs 0%; P = 0.03). CONCLUSION: This study demonstrates no benefit of ED of fetuses with gastroschisis when postnatal gastroschisis management is similar to that used in routine care. Rather, the data suggest that ED is detrimental to infants with gastroschisis. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Parto inducido a las 34 semanas versus atención obstétrica rutinaria en la gastrosquisis fetal: ensayo controlado aleatorizado OBJETIVO: Evaluar si el parto pretérmino inducido (PI) a las 34 semanas es beneficioso para los recién nacidos con gastrosquisis aislada en comparación con la atención obstétrica rutinaria (AR). MÉTODOS: Entre mayo de 2013 y septiembre de 2015, se invitó a participar en este estudio a todas las mujeres con diagnóstico ecográfico de gastrosquisis fetal remitidas a un mismo centro terciario, antes de las 34 semanas de gestación. Las pacientes elegibles fueron asignadas al azar al PI (inducción del parto a las 34 semanas) o a la AR (parto espontáneo a las 37-38 semanas, en función de los indicios obstétricos estándar). La medida de resultado primaria fue la duración de la nutrición parenteral total (NPT). Las medidas de resultado secundarias fueron el tiempo hasta el cierre de la gastrosquisis y la duración de la estancia hospitalaria. Las variables de resultado se compararon mediante métodos estadísticos apropiados. El análisis se basó en la intención de tratar. RESULTADOS: Se evaluó la elegibilidad de 25 mujeres, de las cuales 21 (84%; IC 95%, 63,9-95,5%) aceptaron participar en el estudio; de ellas, 10 fueron asignadas al azar al PI y 11 a la AR. El ensayo se detuvo después del primer análisis provisional planificado debido a preocupaciones sobre la seguridad de las pacientes y por su intrascendencia; por lo tanto, sólo se reclutaron 21 de las 86 pacientes esperadas (24,4%; IC 95%, 15,8-34,9%). La mediana de la edad gestacional en el momento del parto fue de 34,3 (rango: 34-36) semanas en el grupo de PI y 36,7 (rango: 27-38) semanas en el grupo de AR. Una paciente del grupo de PI tuvo un parto a las 36 semanas, después de una inducción infructuosa a las 34 semanas. Los neonatos de las mujeres que se sometieron a PI, comparados con los del grupo de AR, no mostraron diferencias en la mediana del número de días de NPT (54 (rango: 17-248) vs 21 (rango: 9-465) días; P=0,08), número de días hasta el cierre de la gastrosquisis (7 (rango: 0-15) vs 5 (rango: 0-8) días; P=0,28) y duración de la estancia hospitalaria (70,5 (rango: 22-137) vs 31 (rango: 19-186) días; P=0,15). Sin embargo, la probabilidad de experimentar sepsis de inicio tardío fue mayor en los neonatos del grupo de PI en comparación el grupo de AR (40% (IC 95%, 12,2-73,8%) vs 0%; P=0,03). CONCLUSIÓN: Este estudio demuestra que el PI no presenta ningún beneficio para los fetos con gastrosquisis cuando el tratamiento de la gastrosquisis postnatal es similar al utilizado en la atención rutinaria. Más bien, los datos sugieren que el PI es perjudicial para los lactantes con gastrosquisis.

Anatomy transformed.

This paper arose from exhibitions in Oxford and Dublin and comprises three experiments which look at the relationship between anatomy and art. In the first experiment, a passport photograph, photographic portrait and portrait in oils, all of the same sitter, show how artistic input transforms anatomy from a mere likeness into works of art. In the second, the reverse is true, as computer techniques render idealized old master images anatomically accurate. The third experiment addresses the biomechanical consequences of anatomical variation and shows that vehicular design is based on mean body shapes, and so it is the average, rather than the idealized, form that is safer in a collision.

Fetal endoscopic tracheal occlusion reduces pulmonary hypertension in severe congenital diaphragmatic hernia.

OBJECTIVE: Fetal endoscopic tracheal occlusion (FETO) is associated with increased perinatal survival and reduced need for extracorporeal membrane oxygenation (ECMO) in fetuses with severe congenital diaphragmatic hernia (CDH). This study evaluates the impact of FETO on the resolution of pulmonary hypertension (PH) in fetuses with isolated CDH. METHODS: We reviewed retrospectively the medical records of all fetuses evaluated for CDH between January 2004 and July 2017 at a single institution. Fetuses with additional major structural or chromosomal abnormalities were excluded. CDH cases were classified retrospectively into mild, moderate and severe groups based on prenatal magnetic resonance imaging indices (observed-to-expected total fetal lung volume and percentage of intrathoracic liver herniation). Presence of PH was determined based on postnatal echocardiograms. Logistic regression analyses were performed to evaluate the relationship between FETO and resolution of PH by 1 year of age while controlling for side of the CDH, use of ECMO, gestational age at diagnosis, gestational age at delivery, fetal gender, sildenafil use at discharge and CDH severity. Resolution of PH by 1 year of age was compared between a cohort of fetuses with severe CDH that underwent FETO and a cohort that did not have the procedure (non-FETO). A subanalysis was performed restricting the analysis to isolated left CDH. Parametric and non-parametric tests were used for comparisons. RESULTS: Of 257 CDH cases evaluated, 72% (n = 184) had no major structural or chromosomal anomalies of which 58% (n = 107) met the study inclusion criteria. The FETO cohort consisted of 19 CDH cases and the non-FETO cohort (n = 88) consisted of 31 (35%) mild, 32 (36%) moderate and 25 (28%) severe CDH cases. All infants with severe CDH, regardless of whether they underwent FETO, had evidence of neonatal PH. FETO (OR, 3.57; 95% CI, 1.05-12.10; P = 0.041) and ECMO (OR, 5.01; 95% CI, 2.10-11.96; P < 0.001) were independent predictors of resolution of PH by 1 year of age. A higher proportion of infants with severe CDH that underwent FETO had resolution of PH by 1 year after birth compared with infants with severe CDH in the non-FETO cohort (69% (11/16) vs 28% (7/25); P = 0.017). Similar results were observed when the analysis was restricted to cases with left-sided CDH (PH resolution in 69% (11/16) vs 28% (5/18); P = 0.032). CONCLUSION: In infants with severe CDH, FETO and ECMO are independently associated with increased resolution of PH by 1 year of age. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Temporal expression of CD184(CXCR4) and CD171(L1CAM) identifies distinct early developmental stages of human retinal ganglion cells in embryonic stem cell derived retina.

Human retinal ganglion cells (RGCs) derived from pluripotent stem cells (PSCs) have anticipated value for human disease study, drug screening, and therapeutic applications; however, their full potential remains underdeveloped. To characterize RGCs in human embryonic stem cell (hESC) derived retinal organoids we examined RGC markers and surface antigen expression and made comparisons to human fetal retina. RGCs in both tissues exhibited CD184 and CD171 expression and distinct expression patterns of the RGC markers BRN3 and RBPMS. The retinal progenitor cells (RPCs) of retinal organoids expressed CD184, consistent with its expression in the neuroblastic layer in fetal retina. In retinal organoids CD184 expression was enhanced in RGC competent RPCs and high CD184 expression was retained on post-mitotic RGC precursors; CD171 was detected on maturing RGCs. The differential expression timing of CD184 and CD171 permits identification and enrichment of RGCs from retinal organoids at differing maturation states from committed progenitors to differentiating neurons. These observations will facilitate molecular characterization of PSC-derived RGCs during differentiation, critical knowledge for establishing the veracity of these in vitro produced cells. Furthermore, observations made in the retinal organoid model closely parallel those in human fetal retina further validating use of retinal organoid to model early retinal development.

Validation and development of MTH1 inhibitors for treatment of cancer.

BACKGROUND: Previously, we showed cancer cells rely on the MTH1 protein to prevent incorporation of otherwise deadly oxidised nucleotides into DNA and we developed MTH1 inhibitors which selectively kill cancer cells. Recently, several new and potent inhibitors of MTH1 were demonstrated to be non-toxic to cancer cells, challenging the utility of MTH1 inhibition as a target for cancer treatment. MATERIAL AND METHODS: Human cancer cell lines were exposed in vitro to MTH1 inhibitors or depleted of MTH1 by siRNA or shRNA. 8-oxodG was measured by immunostaining and modified comet assay. Thermal Proteome profiling, proteomics, cellular thermal shift assays, kinase and CEREP panel were used for target engagement, mode of action and selectivity investigations of MTH1 inhibitors. Effect of MTH1 inhibition on tumour growth was explored in BRAF V600E-mutated malignant melanoma patient derived xenograft and human colon cancer SW480 and HCT116 xenograft models. RESULTS: Here, we demonstrate that recently described MTH1 inhibitors, which fail to kill cancer cells, also fail to introduce the toxic oxidized nucleotides into DNA. We also describe a new MTH1 inhibitor TH1579, (Karonudib), an analogue of TH588, which is a potent, selective MTH1 inhibitor with good oral availability and demonstrates excellent pharmacokinetic and anti-cancer properties in vivo. CONCLUSION: We demonstrate that in order to kill cancer cells MTH1 inhibitors must also introduce oxidized nucleotides into DNA. Furthermore, we describe TH1579 as a best-in-class MTH1 inhibitor, which we expect to be useful in order to further validate the MTH1 inhibitor concept.

The development of the Hong Kong Heat Index for enhancing the heat stress information service of the Hong Kong Observatory.

This paper presents a study to develop a heat index, for use in hot and humid sub-tropical climate in Hong Kong. The study made use of hospitalization data and heat stress measurement data in Hong Kong from 2007 to 2011. The heat index, which is called Hong Kong Heat Index (HKHI), is calculated from the natural wet bulb temperature, the globe temperature, and the dry bulb temperature together with a set of coefficients applicable to the high humidity condition in the summer of Hong Kong. Analysis of the response of hospitalization rate to variation in HKHI and two other heat indices, namely Wet Bulb Globe Temperature (WBGT) and Net Effective Temperature (NET), revealed that HKHI performed generally better than WBGT and NET in reflecting the heat stress impact on excess hospitalization ratio in Hong Kong. Based on the study results, two reference criteria of HKHI were identified to establish a two-tier approach for the enhancement of the heat stress information service in Hong Kong.

The effect of bisphosphonate treatment on the biochemical and cellular events during bone remodelling in response to microinjury stimulation.

Osteoporosis is one of the most prevalent bone diseases worldwide and is characterised by high levels of bone turnover, a marked loss in bone mass and accumulation of microdamage, which leads to an increased fracture incidence that places a huge burden on global health care systems. Bisphosphonates have been used to treat osteoporosis and have shown great success in conserving bone mass and reducing fracture incidence. In spite of the existing knowledge of the in vivo responses of bone to bisphosphonates, the cellular responses to these drugs have yet to be fully elucidated. In vitro model systems that allow the decoupling of complex highly integrated events, such as bone remodelling, provide a tool whereby these biological processes may be studied in a more simplified context. This study firstly utilised an in vitro model system of bone remodelling and comprising all three major cell types of the bone (osteocytes, osteoclasts and osteoblasts), which was representative of the bone's capacity to sense microdamage and subsequently initiate a basic multicellular unit response. Secondly, this system was used to study the effect of two commonly utilised aminobisphosphonate treatments for osteoporosis, alendronate and zoledronate. We demonstrated that microinjury to osteocyte networks being treated with bisphosphonates modulates receptor activator of nuclear factor kappa-B ligand and osteoprotegerin activity, and subsequently osteoclastogenesis. Furthermore, bisphosphonates increased the osteogenic potential following microinjury. Thus, we have shown for the first time that bisphosphonates act at all three stages of bone remodelling, from microinjury to osteoclastogenesis and ultimately osteogenesis.

Quantification of liver herniation in fetuses with isolated congenital diaphragmatic hernia using two-dimensional ultrasonography.

OBJECTIVES: To describe a method of quantifying the amount of liver herniation in fetuses with isolated congenital diaphragmatic hernia (CDH) using two-dimensional ultrasonography and to correlate this finding with neonatal outcome. METHODS: Ultrasound images obtained from 77 consecutive fetuses that presented with isolated CDH between January 2004 and July 2012 were reviewed. Liver herniation and thoracic area were measured in a cross-sectional plane of the fetal chest at the level of the four-chamber view of the heart (the same section as is used to measure the lung area-to-head circumference ratio) and the ultrasound-derived liver-to-thoracic area ratio (US-LiTR) was calculated by dividing the liver herniation area by the thoracic area. Receiver-operating characteristics (ROC) curve analysis was used to evaluate the performance of US-LiTR in predicting neonatal outcome (survival to 6 months after delivery and need for extracorporeal membrane oxygenation (ECMO)). In addition, the US-LiTR was compared with the magnetic resonance imaging (MRI)-derived volume ratio (MRI-LiTR) and percentage of liver herniation (MRI-%LH). RESULTS: The overall neonatal mortality in the 77 cases with isolated CDH was 20.8% (16/77). ECMO was needed in 35.5% (27/76) of the newborns, with a survival rate of 52%. The US-LiTR was associated statistically with mortality (P < 0.01) and with the need for ECMO (P < 0.01). Good correlations were observed between US-LiTR and MRI-LiTR (r = 0.87; P < 0.001) and between US-LiTR and MRI-%LH (r = 0.90; P < 0.001). Based on ROC curve analysis, all three parameters had similar accuracy in predicting mortality (US-LiTR: area under the ROC curve (AUC), 0.78 (95% CI, 0.65-0.92), P < 0.01; MRI-LiTR: AUC, 0.77 (95% CI, 0.63-0.90), P < 0.01; MRI-%LH: AUC, 0.79 (95% CI, 0.65-0.92), P < 0.01, respectively) as well as the need for ECMO (US-LiTR: AUC, 0.72 (95% CI, 0.60-0.84), P < 0.01; MRI-LiTR: AUC, 0.73 (95% CI, 0.60-0.88), P < 0.01; MRI-%LH: AUC, 0.77 (95% CI, 0.64-0.89), P < 0.01, respectively). CONCLUSIONS: Two-dimensional ultrasound measurement of the amount of liver herniation in fetuses with isolated CDH is feasible and demonstrates a predictive accuracy for neonatal outcome similar to that of MRI.

Congenital heart anomaly in newborns with congenital diaphragmatic hernia: a single-center experience.

OBJECTIVE: To evaluate the impact of the presence of a congenital heart anomaly (CHA) and its potential contribution to morbidity and mortality in infants with congenital diaphragmatic hernia (CDH). METHODS: In this retrospective cohort study, prenatal and postnatal data of all newborns diagnosed with CDH between January 2004 and December 2012 in a single center were reviewed. Cases were classified into two groups: those with 'isolated' CDH and those with both CDH and CHA. Patients with CHA were further subclassified into those with a major or minor CHA based on the Risk Adjustment for Congenital Heart Surgery-1 (RACHS-1), and the Society of Thoracic Surgeons-European Association for Cardiothoracic Surgery (STS-EACTS) scoring systems. Patients with associated non-cardiac anomalies, including 'syndromic cases', were excluded from the analysis. Primary and secondary outcomes were survival up to 1 year of age and a need for extracorporeal membrane oxygenation (ECMO), respectively. RESULTS: Of the 180 infants with CDH, 41 were excluded because of the presence of non-cardiac associated anomalies, 118 had isolated CDH and 21 had CDH with CHA (16 with minor and five with major CHA). Receiver-operating characteristics curve analysis demonstrated that the best cut-off for survival was when the score for CHA was ≤ 2 for both RACHS-1 (area under the curve (AUC), 0.74 (P = 0.04); sensitivity, 80.0%; specificity, 87.5%) and STS-EACTS (AUC, 0.83 (P = 0.03); sensitivity, 100%; specificity, 87.5%). Survival rate at 1 year was significantly lower in those with CHD and a major CHA (40.0%; P = 0.04) than in those with isolated CDH (77.1%) and those with CDH and a minor CHA (81.3%). We found no significant differences among the groups with regard to the need for ECMO. CONCLUSIONS: In general, a milder form of CHA does not appear to have a negative impact on the survival of infants with CDH. However, mortality appears to be significantly higher in infants with CDH and a major form of CHA. The scoring systems appear to be useful as predictors for classifying the effects of CHA in this population of patients.

Fatigue failure of osteocyte cellular processes: implications for the repair of bone.

The physical effects of fatigue failure caused by cyclic strain are important and for most materials well understood. However, nothing is known about this mode of failure in living cells. We developed a novel method that allowed us to apply controlled levels of cyclic displacement to networks of osteocytes in bone. We showed that under cyclic loading, fatigue failure takes place in the dendritic processes of osteocytes at cyclic strain levels as low as one tenth of the strain needed for instantaneous rupture. The number of cycles to failure was inversely correlated with the strain level. Further experiments demonstrated that these failures were not artefacts of our methods of sample preparation and testing, and that fatigue failure of cell processes also occurs in vivo. This work is significant as it is the first time it has been possible to conduct fatigue testing on cellular material of any kind. Many types of cells experience repetitive loading which may cause failure or damage requiring repair. It is clinically important to determine how cyclic strain affects cells and how they respond in order to gain a deeper understanding of the physiological processes stimulated in this manner. The more we understand about the natural repair process in bone the more targeted the intervention methods may become if disruption of the repair process occurred. Our results will help to understand how the osteocyte cell network is disrupted in the vicinity of matrix damage, a crucial step in bone remodelling.

Fetal lung volume and quantification of liver herniation by magnetic resonance imaging in isolated congenital diaphragmatic hernia.

OBJECTIVE: To determine associations between fetal lung and liver herniation volumes measured by magnetic resonance imaging (MRI) and mortality/need for extracorporeal membrane oxygenation (ECMO) in cases of isolated congenital diaphragmatic hernia (CDH). A secondary objective was to compare prenatal MRI parameters with two-dimensional ultrasound lung measurements. METHODS: A retrospective review of medical records of all fetuses with isolated CDH evaluated between January 2004 and July 2012 was performed. The following MRI parameters were measured at 20-32 weeks: observed/expected total fetal lung volume (o/e-TLV), predicted pulmonary volume (PPV), percentage of liver herniated into the fetal thorax (%LH) and the liver/thoracic volume ratio (LiTR). These were compared with the ultrasound-determined lung-to-head ratio (LHR) and the observed/expected LHR (o/e-LHR) in the same cohort. The predictive value of MRI and ultrasound parameters for mortality and the need for ECMO was evaluated by univariate, multivariate and factor analysis and by receiver-operating characteristics curves. RESULTS: Eighty fetuses with isolated CDH were evaluated. Overall mortality was 18/80 (22.5%). Two newborns died a few hours after birth. ECMO was performed in 29/78 (37.2%) newborns, with a survival rate of 48.3% (14/29). The side of the diaphragmatic defect was not associated with mortality (P = 0.99) or the need for ECMO (P = 0.48). Good correlation was observed among o/e-TLV, PPV, LHR and o/e-LHR as well as between %LH and LiTR (r = 0.89; P < 0.01); however, fetal lung measurements and measures of liver herniation were not correlated (all P > 0.05). All parameters were statistically associated with mortality or the need for ECMO. The best combination of measurements to predict mortality was o/e-TLV and %LH, with 83% accuracy. CONCLUSION: Mortality and the need for ECMO in neonates with isolated CDH can be best predicted using a combination of MRI o/e-TLV and %LH.

Realgar (As4S4) nanoparticles and arsenic trioxide (As2O3) induced autophagy and apoptosis in human melanoma cells in vitro.

The aim of the present study was to compare the effect of realgar nanoparticles and arsenic trioxide (ATO) on viability, DNA damage, proliferation, autophagy and apoptosis in the human melanoma cell lines BOWES and A375. The application of various flow cytometric methods for measurements cell viability, DNA cell cycle, mitochondrial potential, lysosomal activity, and intracellular content of glutathione was used. In addition, quantitative PCR, western blotting and multiplex bead array analyses were applied for evaluation of redox stress, autophagic flux, and cell signaling alterations.The results showed that realgar treatment of studied cells caused modulation of cell proliferation, induced a block in G2/M phase of the cell cycle and altered phosphorylation of IκB, Akt, ERK1/2, p38, and JNK kinases, as well as decreased mitochondrial membrane potential. Additionally, it appeared that induction of cell death by both realgar and ATO was dose-dependent, when lower (0.3 µM) dosage increased lysosomal activity and induced autophagy and higher (1.25 µM) concentration resulted in the appearance of apoptosis, while pan-caspase inhibitor attenuated more efficiently realgar- than ATO-induced cell death. Furthermore, low concentrations of ATO and realgar nanoparticles increased the content of intracellular glutathione and elevated γ-H2AX expression confirmed DNA damage preferentially at higher concentrations of both drugs used. Further analysis revealed slight differences in time-dependent phosphorylation pattern due to both realgar and ATO treatments, while significant differences were noticed between cell lines. In conclusion, realgar nanoparticles and ATO treatment induced dose-dependent activation of autophagy and apoptosis in both melanoma cell lines, when autophagy flux was determined at lower drug concentrations and the switch to apoptosis occurred at higher concentrations of both arsenic forms.

Rotavirus activity and meteorological variations in an Asian subtropical city, Hong Kong, 1995-2009.

Rotavirus is a leading cause of severe infectious diarrhea in infants and young children aged <5 years. Rotavirus infections have minimal to strong seasonality depending on geographical locations. In this study, a comprehensive retrospective analysis was performed to evaluate the association between rotavirus admission and multiple key meteorological variables, including air temperature, relative humidity, atmospheric pressure, and solar radiation over a 15-year period from 1995 to 2009 in Hong Kong. Rotavirus infections were found to show a distinct cyclical pattern with an annual peak in cold season. The weekly number of cases showed the strongest correlation with average air temperature of the previous 7 days (rho=-0.69; P<0.0001), followed by atmospheric pressure (rho=+0.67; P<0.0001); whereas only weak correlation with relative humidity (rho=-0.252; P<0.0001) and solar radiation (rho=-0.312; P<0.0001) was observed. Curve fitting regression analysis suggested that the correlation was nonlinear in nature in which the effect was more profound towards lower air temperature and higher atmospheric pressure conditions. In binary logistic regression analysis, a final model that included air temperature (≤ 20°C) and atmospheric pressure (≥ 1,013 hPa) predicted correctly 85.3% and 82.6% of weeks with rotavirus activity above and below the baseline level, respectively. In multivariate Poisson model, air temperature and solar radiation were independent factors associated with the weekly number of rotavirus cases, adjusted for seasonal variation. In summary, the current study provides evidence suggesting that local seasonal activity of rotavirus correlated strongly with air temperature, followed by atmospheric pressure but only minimally with relative humidity in pre-vaccine era.

Examination of osteoarthritis and subchondral bone alterations within the stifle joint of an ovariectomised ovine model.

The exact relationship between osteoporosis and osteoarthritis is still a matter for debate for many. The ovariectomised ewe is frequently used as a model for osteoporosis, resulting in significant alterations in bone morphometry and turnover in both trabecular and subchondral bone after 1 year. This study examines whether ovariectomy has any impact on development of osteoarthritis within the ovine stifle joint at the same time point. In addition, we investigate whether there are any significant correlations present between articular cartilage degeneration and alterations in microstructural parameters or turnover rates in the underlying bone. Twenty-two sheep were examined in this study; 10 of the sheep underwent ovariectomy and 12 were kept as controls. Five distinctive fluorochrome dyes were administered intravenously at 12-week intervals to both groups, to label sites of bone turnover. All animals were then sacrificed 12 months postoperatively. Although most specimens showed some evidence of osteoarthritis, no measurable difference between the two study groups was detected. Osteoarthritis was associated with a thinning of the subchondral plate, specifically the subchondral cortical bone; however, whereas previous studies have suggested a link between trabecular thinning and osteoarthritis, this was not confirmed. No correlation was found between osteoarthritis and bone turnover rates of either the subchondral trabecular bone or bone plate. In conclusion, despite the fact that ovariectomy results in marked morphological and structural changes in the ovine stifle joint at 1-year postoperatively, no evidence was found to suggest that it plays a direct role in the aetiology of osteoarthritis.