Feasibility of Photofrin II as a radiosensitizing agent in solid tumors - Preliminary results

Background: Photofrin II has been demonstrated to serve as a specific and selective radiosensitizing agent in in vitro and in vivo tumor models. We aimed to investigate the feasibility of a clinical application of Photofrin II. Material and Methods: 12 patients were included in the study (7 unresectable solid tumors of the pelvic region, 3 malignant gliomas, 1 recurrent oropharyngeal cancer, 1 recurrent adenocarcinoma of the sphenoid sinus). The dose of ionizing irradiation was 30-50.4 Gy; a boost irradiation of 14 Gy was added for the pelvic region. All patients were intravenously injected with 1 mg/kg Photofrin II 24 h prior to the commencement of radiotherapy. Magnetic resonance imaging (MRI) controls and in some cases positron emission tomography (PET) were performed in short intervals. The mean follow-up was 12.9 months. Results: No major adverse events were noted. Minor adverse events consisted of mild diarrhea, nausea and skin reactions. A complete remission was observed in 4/12 patients. A reduction in local tumor volume of > 45% was achieved in 4/12 patients. Stable disease was observed in 4/12 patients. 1 patient showed local disease progression after 5 months. Conclusion: The early follow-up results are encouraging regarding the feasibility of the application of Photofrin II as a radiosensitizing agent

Skeletal muscle, haematological and splenic volume characteristics of elite breath-hold divers

Purpose The aim of the study was to provide an evaluation of the oxygen transport, exchange and storage capacity of elite breath-hold divers (EBHD) compared with non-divers (ND). Methods Twenty-one healthy males’ (11 EBHD; 10 ND) resting splenic volumes were assessed by ultrasound and venous blood drawn for full blood count analysis. Percutaneous skeletal muscle biopsies were obtained from the m. vastus lateralis to measure capillarisation, and fibre type-specific localisation and distribution of myoglobin and mitochondrial content using quantitative immunofluorescence microscopy. Results Splenic volume was not different between groups. Reticulocytes, red blood cells and haemoglobin concentrations were higher (+ 24%, p < 0.05; + 9%, p < 0.05; + 3%, p < 0.05; respectively) and mean cell volume was lower (− 6.5%, p < 0.05) in the EBHD compared with ND. Haematocrit was not different between groups. Capillary density was greater (+ 19%; p < 0.05) in the EBHD. The diffusion distance (R95) was lower in type I versus type II fibres for both groups (EBHD, p < 0.01; ND, p < 0.001), with a lower R95 for type I fibres in the EBHD versus ND (− 13%, p < 0.05). Myoglobin content was higher in type I than type II fibres in EBHD (+ 27%; p < 0.01) and higher in the type I fibres of EBHD than ND (+ 27%; p < 0.05). No fibre type differences in myoglobin content were observed in ND. Mitochondrial content was higher in type I than type II fibres in EBHD (+ 35%; p < 0.05), with no fibre type differences in ND or between groups. Conclusions In conclusion, EBDH demonstrate enhanced oxygen storage in both blood and skeletal muscle and a more efficient oxygen exchange capacity between blood and skeletal muscle versus ND

Three-Compartment Body Composition Changes in Professional Rugby Union Players Over One Competitive Season : A Team and Individualized Approach

The purpose of this study was to investigate longitudinal body composition of professional rugby union players over one competitive season. Given the potential for variability in changes, and as the first to do so, we conducted individual analysis in addition to analysis of group means. Thirty-five professional rugby union players from one English Premiership team (forwards: n = 20, age: 25.5 ± 4.7 years; backs: n = 15, age: 26.1 ± 4.5 years) received one total-body dual-energy X-ray absorptiometry (DXA) scan at preseason (August), midseason (January) and endseason (May), enabling quantification of body mass, total and regional fat mass, lean mass, percentage tissue fat mass (%TFM) and bone mineral content (BMC). Individual analysis was conducted by applying least significant change (LSC), derived from our previously published precision data and in accordance with International Society for Clinical Densitometry (ISCD) guidelines. Mean body mass remained stable throughout the season (p > 0.05), but total fat mass and %TFM increased from pre to endseason, and mid to endseason (p < 0.05). There were also statistically significant increases in total-body BMC across the season (p < 0.05). In both groups, there was a loss of lean mass between mid and endseason (p < 0.018). Individual evaluation using LSC and Bland-Altman analysis revealed a meaningful loss of lean mass in 17 players and a gain of fat mass in 21 players from pre to endseason. Twelve players had no change and there were no differences by playing position. There were individual gains or no net changes in BMC across the season for 10 and 24 players, respectively. This study highlights the advantages of an individualised approach to DXA body composition monitoring and this can be achieved through application of derived LSC

Treatment of chronic anterior shoulder dislocation by open reduction and simultaneous Bankart lesion repair

<p>Abstract</p> <p>Background</p> <p>Untreated chronic shoulder dislocation eventually leads to functional disability and pain. Open reduction with different fixation methods have been introduced for most chronic shoulder dislocation. We hypothesized that open reduction and simultaneous Bankart lesion repair in chronic anterior shoulder dislocation obviates the need for joint fixation and leads to better results than previously reported methods.</p> <p>Methods</p> <p>Eight patients with chronic anterior dislocation of shoulder underwent open reduction and capsulolabral complex repair after an average delay of 10 weeks from injury. Early motion was allowed the day after surgery in the safe position and the clinical and radiographic results were analyzed at an average follow-up of one year.</p> <p>Results</p> <p>The average Rowe and Zarin's score was 86 points. Four out of eight shoulders were graded as excellent, three as good and one as fair (Rowe and Zarins system). All patients were able to perform their daily activities and they had either mild or no pain. Anterior active forward flexion loss averaged 18 degrees, external active rotation loss averaged 17.5 degrees and internal active rotation loss averaged 3 vertebral body levels. Mild degenerative joint changes were noted in one patient.</p> <p>Conclusion</p> <p>The results show that the overall prognosis for this method of operation is more favorable than the previously reported methods and we recommend concomitant open reduction and capsulolabral complex repair for the treatment of old anterior shoulder dislocation.</p> <p>Level of Evidence</p> <p>Therapeutic study, Level IV (case series [no, or historical, control group])</p

Antenatal risk factors for postnatal depression: a prospective study of chinese women at maternal and child health centres

Background: Risk factors for postnatal depression (PND) are under-explored in the Chinese populations. There is increasing recognition of the importance of identifying predictive factors during the antenatal period for PND. The present study aimed to identify the risk factors for postnatal depression in a community cohort of Chinese women with special focus on the antenatal risk factors.Methods: Eight hundred and five Chinese women were interviewed during their third trimester of pregnancy and at around 2 months postnatally. Putative risk factors for PND were collected and the diagnosis of PND was confirmed by the Structured Clinical Interview for DSM-IV Axis I Disorders. The 2-month postnatal depression status was used as the dependent variable for univariate and multivariate analyses against putative risk factors.Results: Marital dissatisfaction (Relative Risk = 8.27), dissatisfied relationship with mother-in-law (Relative Risk = 3.93), antenatal depressive symptomatology (Relative Risk = 3.90), and anxiety-prone personality (Relative Risk = 2.14) predicted PND in Chinese women independently.Conclusions: Chinese women tend to keep their own feelings and emotions and it is important to monitor Chinese pregnant women with these predictive risk factors so that PND can be identified early. © 2012 Siu et al; licensee BioMed Central Ltd.published_or_final_versio

Restricted fluid bolus volume in early septic shock: Results of the Fluids in Shock pilot trial

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ. Objective To determine the feasibility of Fluids in Shock, a randomised controlled trial (RCT) of restricted fluid bolus volume (10 mL/kg) versus recommended practice (20 mL/kg). Design Nine-month pilot RCT with embedded mixed-method perspectives study. Setting 13 hospitals in England. Patients Children presenting to emergency departments with suspected infection and shock after 20 mL/kg fluid. Interventions Patients were randomly allocated (1:1) to further 10 or 20 mL/kg fluid boluses every 15 min for up to 4 hours if still in shock. Main outcome measures These were based on progression criteria, including recruitment and retention, protocol adherence, separation, potential trial outcome measures, and parent and staff perspectives. Results Seventy-five participants were randomised; two were withdrawn. 23 (59%) of 39 in the 10 mL/kg arm and 25 (74%) of 34 in the 20 mL/kg arm required a single trial bolus before the shock resolved. 79% of boluses were delivered per protocol in the 10 mL/kg arm and 55% in the 20 mL/kg arm. The volume of study bolus fluid after 4 hours was 44% lower in the 10 mL/kg group (mean 14.5 vs 27.5 mL/kg). The Paediatric Index of Mortality-2 score was 2.1 (IQR 1.6-2.7) in the 10 mL/kg group and 2.0 (IQR 1.6-2.5) in the 20 mL/kg group. There were no deaths. Length of hospital stay, paediatric intensive care unit (PICU) admissions and PICU-free days at 30 days did not differ significantly between the groups. In the perspectives study, the trial was generally supported, although some problems with protocol adherence were described. Conclusions Participants were not as unwell as expected. A larger trial is not feasible in its current design in the UK. Trial registration number ISRCTN15244462

Relative changes in brain and kidney biomarkers with Exertional Heat Illness during a cool weather marathon

BACKGROUND: Medical personnel may find it challenging to distinguish severe Exertional Heat Illness (EHI), with attendant risks of organ-injury and longer-term sequalae, from lesser forms of incapacity associated with strenuous physical exertion. Early evidence for injury at point-of-incapacity could aid the development and application of targeted interventions to improve outcomes. We aimed to investigate whether biomarker surrogates for end-organ damage sampled at point-of-care (POC) could discriminate EHI versus successful marathon performance. METHODS: Eight runners diagnosed as EHI cases upon reception to medical treatment facilities and 30 successful finishers of the same cool weather marathon (ambient temperature 8 rising to 12 ºC) were recruited. Emerging clinical markers associated with injury affecting the brain (neuron specific enolase, NSE; S100 calcium-binding protein B, S100β) and renal system (cystatin C, cysC; kidney-injury molecule-1, KIM-1; neutrophil gelatinase-associated lipocalin, NGAL), plus copeptin as a surrogate for fluid-regulatory stress, were sampled in blood upon marathon collapse/completion, as well as beforehand at rest (successful finishers only). RESULTS: Versus successful finishers, EHI showed significantly higher NSE (10.33 [6.37, 20.00] vs. 3.17 [2.71, 3.92] ug.L-1, P<0.0001), cysC (1.48 [1.10, 1.67] vs. 1.10 [0.95, 1.21] mg.L-1, P = 0.0092) and copeptin (339.4 [77.0, 943] vs. 18.7 [7.1, 67.9] pmol.L-1, P = 0.0050). Discrimination of EHI by ROC (Area-Under-the-Curve) showed performance that was outstanding for NSE (0.97, P<0.0001) and excellent for copeptin (AUC = 0.83, P = 0.0066). CONCLUSIONS: As novel biomarker candidates for EHI outcomes in cool-weather endurance exercise, early elevations in NSE and copeptin provided sufficient discrimination to suggest utility at point-of-incapacity. Further investigation is warranted in patients exposed to greater thermal insult, followed up over a more extended period

The Association between Pro-Social Attitude and Reproductive Success Differs between Men and Women

The evolution of pro-social attitude and cooperation in humans is under debate. Most of the knowledge on human cooperation results from laboratory experiments and theoretic modeling. Evolutionary explanations, however, rest upon fitness consequences. We therefore examined fitness correlates of pro-social behavior in a real life setting, analyzing data from the Wisconsin Longitudinal Study (n = 2545 men, 2967 women). We investigated whether pro-social attitude, proxied by self reported voluntary work, is associated with lifetime reproductive success. We find a sex difference in the association between pro-social attitude and offspring number. In men, a pro-social attitude was associated with higher offspring number, whereas in women, it was associated with lower offspring count. To our knowledge, this is the first study to demonstrate fitness consequences of pro-social behavior towards strangers. We conclude that analysing real life settings may help to explain the evolutionary forces leading to pro-social behavior in humans and speculate that these factors might differ between the sexes

Fecal Microbiota in Premature Infants Prior to Necrotizing Enterocolitis

Intestinal luminal microbiota likely contribute to the etiology of necrotizing enterocolitis (NEC), a common disease in preterm infants. Microbiota development, a cascade of initial colonization events leading to the establishment of a diverse commensal microbiota, can now be studied in preterm infants using powerful molecular tools. Starting with the first stool and continuing until discharge, weekly stool specimens were collected prospectively from infants with gestational ages ≤32 completed weeks or birth weights≤1250 g. High throughput 16S rRNA sequencing was used to compare the diversity of microbiota and the prevalence of specific bacterial signatures in nine NEC infants and in nine matched controls. After removal of short and low quality reads we retained a total of 110,021 sequences. Microbiota composition differed in the matched samples collected 1 week but not <72 hours prior to NEC diagnosis. We detected a bloom (34% increase) of Proteobacteria and a decrease (32%) in Firmicutes in NEC cases between the 1 week and <72 hour samples. No significant change was identified in the controls. At both time points, molecular signatures were identified that were increased in NEC cases. One of the bacterial signatures detected more frequently in NEC cases (p<0.01) matched closest to γ-Proteobacteria. Although this sequence grouped to the well-studied Enterobacteriaceae family, it did not match any sequence in Genbank by more than 97%. Our observations suggest that abnormal patterns of microbiota and potentially a novel pathogen contribute to the etiology of NEC

Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development.

BACKGROUND: We present the genome sequence of the tammar wallaby, Macropus eugenii, which is a member of the kangaroo family and the first representative of the iconic hopping mammals that symbolize Australia to be sequenced. The tammar has many unusual biological characteristics, including the longest period of embryonic diapause of any mammal, extremely synchronized seasonal breeding and prolonged and sophisticated lactation within a well-defined pouch. Like other marsupials, it gives birth to highly altricial young, and has a small number of very large chromosomes, making it a valuable model for genomics, reproduction and development. RESULTS: The genome has been sequenced to 2 × coverage using Sanger sequencing, enhanced with additional next generation sequencing and the integration of extensive physical and linkage maps to build the genome assembly. We also sequenced the tammar transcriptome across many tissues and developmental time points. Our analyses of these data shed light on mammalian reproduction, development and genome evolution: there is innovation in reproductive and lactational genes, rapid evolution of germ cell genes, and incomplete, locus-specific X inactivation. We also observe novel retrotransposons and a highly rearranged major histocompatibility complex, with many class I genes located outside the complex. Novel microRNAs in the tammar HOX clusters uncover new potential mammalian HOX regulatory elements. CONCLUSIONS: Analyses of these resources enhance our understanding of marsupial gene evolution, identify marsupial-specific conserved non-coding elements and critical genes across a range of biological systems, including reproduction, development and immunity, and provide new insight into marsupial and mammalian biology and genome evolution