Predictors of Quality of Life Decline in Patients with Oligometastases treated with Stereotactic Ablative Radiotherapy: Analysis of the Population-Based SABR-5 Phase II Trial.

AIMS: Most patients experience stable quality of life (QoL) after stereotactic ablative radiotherapy (SABR) treatment for oligometastases. However, a subset of patients experience clinically relevant declines in QoL on post-treatment follow-up. This study aimed to identify risk factors for QoL decline. MATERIALS AND METHODS: The SABR-5 trial was a population-based single-arm phase II study of SABR to up to five sites of oligometastases. Prospective QoL was measured using treatment site-specific tools at pre-treatment baseline and 3, 6, 9, 12, 15, 18, 21, 24, 30 and 36 months after treatment. The time to persistent QoL decline was calculated as the time from SABR to the first decline in QoL score meeting minimum clinically important difference with no improvement to baseline score on subsequent assessments. Univariable and multivariable logistic regression analyses were carried out to determine factors associated with QoL decline. RESULTS: One hundred and thirty-three patients were included with a median follow-up of 32 months (interquartile range 25-43). Thirty-five patients (26%) experienced a persistent decline in QoL. The median time until persistent QoL decline was not reached. The cumulative incidence of QoL decline at 2 and 3 years were 22% (95% confidence interval 14.0-29.6) and 40% (95% confidence interval 28.0-51.2), respectively. In multivariable analysis, disease progression (odds ratio 5.23, 95% confidence interval 1.59-17.47, P = 0.007) and adrenal metastases (odds ratio 9.70, 95% confidence interval 1.41-66.93, P = 0.021) were associated with a higher risk of QoL decline. Grade 3 or higher (odds ratio 3.88, 95% confidence interval 0.92-16.31, P = 0.064) and grade 2 or higher SABR-associated toxicity (odds ratio 2.24, 95% confidence interval 0.85-5.91, P = 0.10) were associated with an increased risk of QoL decline but did not reach statistical significance. CONCLUSIONS: Disease progression and adrenal lesion site were associated with persistent QoL decline following SABR. The development of grade 3 or higher toxicities was also associated with an increased risk, albeit not statistically significant. Further studies are needed, focusing on the QoL impact of metastasis-directed therapies.

Prospective Longitudinal Assessment of Quality of Life After Stereotactic Ablative Radiotherapy for Oligometastases: Analysis of the Population-based SABR-5 Phase II Trial.

AIMS: To evaluate longitudinal patient-reported quality of life (QoL) in patients treated with stereotactic ablative radiotherapy (SABR) for oligometastases. MATERIALS AND METHODS: The SABR-5 trial was a population-based single-arm phase II study of SABR to up to five sites of oligometastases, conducted in six regional cancer centres in British Columbia, Canada from 2016 to 2020. Prospective QoL was measured using treatment site-specific QoL questionnaires at pre-treatment baseline and at 3, 6, 9, 12, 15, 18, 21, 24, 30 and 36 months after treatment. Patients with bone metastases were assessed with the Brief Pain Inventory (BPI). Patients with liver, adrenal and abdominopelvic lymph node metastases were assessed with the Functional Assessment of Chronic Illness Therapy-Abdominal Discomfort (FACIT-AD). Patients with lung and intrathoracic lymph node metastases were assessed with the Prospective Outcomes and Support Initiative (POSI) lung questionnaire. The two one-sided test procedure was used to assess equivalence between the worst QoL score and the baseline score of individual patients. The mean QoL at all time points was used to determine the trajectory of QoL response after SABR. The proportion of patients with 'stable', 'improved' or 'worsened' QoL was determined for all time points based on standard minimal clinically important differences (MCID; BPI worst pain = 2, BPI functional interference score [FIS] = 0.5, FACIT-AD Trial Outcome Index [TOI] = 8, POSI = 3). RESULTS: All enrolled patients with baseline QoL assessment and at least one follow-up assessment were analysed (n = 133). On equivalence testing, the patients' worst QoL scores were clinically different from baseline scores and met MCID (BPI worst pain mean difference: 1.8, 90% confidence interval 1.19 to 2.42]; BPI FIS mean difference: 1.68, 90% confidence interval 1.15 to 2.21; FACIT-AD TOI mean difference: -8.76, 90% confidence interval -11.29 to -6.24; POSI mean difference: -4.61, 90% confidence interval -6.09 to -3.14). However, the mean FIS transiently worsened at 9, 18 and 21 months but eventually returned to stable levels. The mean FACIT and POSI scores also worsened at 36 months, albeit with a limited number of responses (n = 4 and 8, respectively). Most patients reported stable QoL at all time points (range: BPI worst pain 71-82%, BPI FIS 45-78%, FACIT-AD TOI 50-100%, POSI 25-73%). Clinically significant stability, worsening and improvement were seen in 70%/13%/18% of patients at 3 months, 53%/28%/19% at 18 months and 63%/25%/13% at 36 months. CONCLUSIONS: Transient decreases in QoL that met MCID were seen between patients' worst QoL scores and baseline scores. However, most patients experienced stable QoL relative to pre-treatment levels on long-term follow-up. Further studies are needed to characterise patients at greatest risk for decreased QoL.

Chromothripsis orchestrates leukemic transformation in blast phase MPN through targetable amplification of DYRK1A.

Chromothripsis, the process of catastrophic shattering and haphazard repair of chromosomes, is a common event in cancer. Whether chromothripsis might constitute an actionable molecular event amenable to therapeutic targeting remains an open question. We describe recurrent chromothripsis of chromosome 21 in a subset of patients in blast phase of a myeloproliferative neoplasm (BP-MPN), which alongside other structural variants leads to amplification of a region of chromosome 21 in ∼25% of patients ('chr21amp'). We report that chr21amp BP-MPN has a particularly aggressive and treatment-resistant phenotype. The chr21amp event is highly clonal and present throughout the hematopoietic hierarchy. DYRK1A , a serine threonine kinase and transcription factor, is the only gene in the 2.7Mb minimally amplified region which showed both increased expression and chromatin accessibility compared to non-chr21amp BP-MPN controls. We demonstrate that DYRK1A is a central node at the nexus of multiple cellular functions critical for BP-MPN development, including DNA repair, STAT signalling and BCL2 overexpression. DYRK1A is essential for BP-MPN cell proliferation in vitro and in vivo , and DYRK1A inhibition synergises with BCL2 targeting to induce BP-MPN cell apoptosis. Collectively, these findings define the chr21amp event as a prognostic biomarker in BP-MPN and link chromothripsis to a druggable target.

[Acute abdomen-Rare cause in an 80-year-old female patient under immunosuppressive treatment]. / Akutes Abdomen ­ seltene Ursache bei einer 80-jährigen Patientin unter immunsuppressiver Therapie.

An 80-year-old woman presented to the emergency department due to abdominal pain. She had a history of opportunistic pneumonia under the effects of immunosuppression after the diagnosis of autoimmune hepatitis. The imaging showed an omental cake formation and the suspicion of peritoneal carcinomatosis. The patient developed an acute abdomen during the hospital stay, followed by exploratory laparotomy. In the presence of extensive intra-abdominal abscess formation both surgically acquired material and blood culture revealed disseminated nocardiosis. The course was fatal due to fulminant septic shock.

The Yin and Yang of ERBB4: Tumor Suppressor and Oncoprotein.

ERBB4 (HER4) is a member of the ERBB family of receptor tyrosine kinases, a family that includes the epidermal growth factor receptor (EGFR/ERBB1/HER1), ERBB2 (Neu/HER2), and ERBB3 (HER3). EGFR and ERBB2 are oncoproteins and validated targets for therapeutic intervention in a variety of solid tumors. In contrast, the role that ERBB4 plays in human malignancies is ambiguous. Thus, here we review the literature regarding ERBB4 function in human malignancies. We review the mechanisms of ERBB4 signaling with an emphasis on mechanisms of signaling specificity. In the context of this signaling specificity, we discuss the hypothesis that ERBB4 appears to function as a tumor suppressor protein and as an oncoprotein. Next, we review the literature that describes the role of ERBB4 in tumors of the bladder, liver, prostate, brain, colon, stomach, lung, bone, ovary, thyroid, hematopoietic tissues, pancreas, breast, skin, head, and neck. Whenever possible, we discuss the possibility that ERBB4 mutants function as biomarkers in these tumors. Finally, we discuss the potential roles of ERBB4 mutants in the staging of human tumors and how ERBB4 function may dictate the treatment of human tumors. SIGNIFICANCE STATEMENT: This articles reviews ERBB4 function in the context of the mechanistic model that ERBB4 homodimers function as tumor suppressors, whereas ERBB4-EGFR or ERBB4-ERBB2 heterodimers act as oncogenes. Thus, this review serves as a mechanistic framework for clinicians and scientists to consider the role of ERBB4 and ERBB4 mutants in staging and treating human tumors.

Persistent Barriers to Smoking Cessation Among Urban, Underserved Women: A Feasibility Study of Tailored Barriers Text Messages.

OBJECTIVES: Despite health risks for themselves and their children, urban underserved women smoke at high rates postpartum. The postpartum period is a stressful transition time that presents unique barriers to sustained cessation. There is limited extant evidence of efficacious psychosocial programs to maintain postpartum smoking cessation. METHODS: Guided by the Cognitive-Social Health Information Processing model, we explored the feasibility of TxT2Commit, a text-messaging intervention designed to prevent postpartum smoking relapse. Participants (n = 43) received supportive cessation-focused text messages for one month postpartum. Using a convergent mixed method design, surveys and interviews assessed changes in psychosocial factors and smoking status through a three month follow-up. RESULTS: Participants reported satisfaction with TxT2Commit, rating text messages as helpful, understandable, supportive, and not bothersome. However, a majority of women (n = 28, 65.1%) relapsed by three months. Participants who stayed smoke free (i.e., non-relapsers) reported significantly less temptation to smoke at one and three months postpartum compared to relapsers (ps < .01). While relapsers had significantly less temptation at one month compared to baseline, temptation increased by three months (p < .01). Consistent with the quantitative results, qualitative interviews identified informational and coping needs, with continued temptation throughout the three months. Non-relapsers were able to manage temptation and reported greater support. CONCLUSIONS FOR PRACTICE: TxT2Commit demonstrates preliminary feasibility and acceptability among urban, underserved postpartum women. However, most participants relapsed by three months postpartum. Additional research is needed to identify targeted messaging to best help women avoid temptation and bolster support to stay smoke free in this uniquely stressful period.

Pulmonary Lymphangioleiomyomatosis originates in the pleural mesothelial cell population.

Lymphangioleiomyomatosis (LAM) is a cystic lung disease mainly affecting women, in which degradation of the lung parenchyma is associated with a cell of unknown provenance, known as a LAM cell. LAM cells carry TSC2 mutations and can be identified in the lung parenchyma by their expression of both smooth muscle actin and antigens characteristic of melanocytes and melanocytic tumors. The nature of the cell-of-origin of LAM is controversial, and despite continued research effort remains elusive. Further, it has not been possible to culture pulmonary LAM cells in vitro, and current research relies on cells and animal models which may not recapitulate all features of the disease. We noted aberrant expression of melanoma antigens in pleural mesothelial cells in lung tissue from LAM patients, indicating that these cells could be the precursors of parenchymal LAM cells. We hypothesise that loss of tuberin function following TSC2 mutation in the mesothelial cell lineage gives rise to the cell-of-origin of pulmonary LAM (P-LAM), and of other associated conditions commonly noted in LAM patients. The unique properties of mesothelial cells provide a straightforward explanation of the diverse presentation of LAM.

Long-term postnatal outcome of fetuses with prenatally suspected septo-optic dysplasia.

OBJECTIVES: Septo-optic dysplasia (SOD) is a clinical syndrome characterized by varying combinations of optic nerve hypoplasia, pituitary gland hypoplasia and abnormal cavum septi pellucidi. It is suspected on prenatal imaging when there is non-visualization or hypoplasia of the septal leaflets. Long-term postnatal outcomes of fetuses with prenatally suspected SOD have been documented poorly. The aims of this study were to describe the natural history of deficient septal leaflets, to quantify the incidence of postnatally confirmed SOD and to document the visual, endocrine and long-term neurodevelopmental outcomes of these infants. METHODS: This was an observational retrospective study of all fetuses with prenatal imaging showing isolated septal agenesis, assessed at a single tertiary center over an 11-year period. Pregnancy, delivery and neonatal outcomes and pre- and postnatal imaging findings were reviewed. Neonatal evaluations or fetal autopsy reports were assessed for confirmation of SOD. Ophthalmologic, endocrine, genetic and long-term developmental evaluations were assessed. Imaging findings and outcome were compared between infants with and those without postnatally confirmed SOD. RESULTS: Of 214 fetuses presenting with septal absence on prenatal ultrasound and magnetic resonance imaging (MRI), 18 (8.4%) were classified as having suspected isolated septal agenesis suspicious for SOD. Uniform prenatal MRI findings in cases with suspected SOD included remnants of the leaflets of the cavum septi pellucidi, fused forniceal columns, normal olfactory bulbs and tracts and a normal optic chiasm. Twelve fetuses were liveborn and five (27.8%) had postnatally confirmed SOD. Only two of these five fetuses had additional prenatal imaging features (pituitary cyst, microphthalmia and optic nerve hypoplasia) supporting a diagnosis of SOD. The other three confirmed SOD cases had no predictive prenatal or postnatal imaging findings that reliably differentiated them from cases without confirmed SOD. Visual and endocrine impairments were present in two (40%) and four (80%) cases with confirmed SOD, respectively. In those with visual and/or endocrine impairment, developmental delay (median age at follow-up, 2.5 (interquartile range, 2.5-7.0) years) was common (80%) and mostly severe. Neonates with isolated septal agenesis and a lack of visual or endocrine abnormalities to confirm SOD had normal development. CONCLUSIONS: Only a quarter of fetuses with isolated septal agenesis suggestive of SOD will have postnatal confirmation of the diagnosis. Clinical manifestations of SOD are variable, but neurodevelopmental delay may be more prevalent than thought formerly. © 2020 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

An electronic patient-reported outcomes measurement system in paediatric orthopaedics.

PURPOSE: The purpose of the study was to evaluate the reliability, review differences and assess patient satisfaction of electronic patient-reported outcome measures (PROMs) compared with paper PROMs. METHODS: Participants between 12 and 19 years of age with a knee-related primary complaint were randomized into two groups. Group 1 completed paper PROMs followed by electronic, while Group 2 received the electronic followed by paper. PROMs included the Pediatric International Knee Documentation Committee (Pedi-IKDC), Hospital for Special Surgery (HSS) Pediatric Functional Activity Brief Scale (HSS Pedi-FABS), Tegner Activity Level Scale, Visual Analogue Scale (VAS), PedsQL Teen and a satisfaction survey. RESULTS: In all, 87 participants were enrolled with one excluded due to incomplete PROMs. Of the 86 participants, 54 were female and 32 were male with an average age of 14.3 years (12 to 18). A high degree of reliability was found when comparing the paper and electronic versions of the Pedi-IKDC (0.946; p < 0.001), HSS Pedi-FABS (0.923; p < 0.001), PedsQL Teen (0.894; p < 0.001), Tegner Activity Level Scale before injury (0.848; p < 0.001) and the Tegner Activity Level Scale after (0.930; p < 0.001). Differences were noted between the VAS scores, with paper scores being significantly higher than electronic (5.3 versus 4.6; p < 0.001). While not significant, a trend was noted in which electronic PROMs took, overall, less time than paper (10.0 mins versus 11.2 mins; p = 0.096).Of all participants, 69.8% preferred the electronic PROMs, 67.4% felt they were faster, 93.0% stated they would complete forms at home prior to appointments and 91.8% were not concerned about the safety/privacy of electronic forms. CONCLUSION: PROMs captured electronically were reliable when compared with paper. Electronic PROMs may be quicker, will not require manual scoring and are preferred by patients. LEVEL OF EVIDENCE: II.

Comparison of gait kinematics in total and unicondylar knee replacement surgery.

INTRODUCTION: This study is aimed to compare kinematic gait data of patients who have undergone total and unicondylar knee replacement. MATERIALS AND METHODS: This single-surgeon retrospective cohort study evaluated 13 patients with unilateral total knee arthroplasty (TKA) and 14 unicondylar knee arthroplasty (UKA). Gait analysis was carried out using a Vicon motion analysis system. The limits of knee flexion during stance phase, at heel strike and at loading response were measured. RESULTS: The total range of motion of the UKA knees was significantly greater than the TKA knees. UKA knees exhibited significantly greater knee extension during the stance phase than the TKA knees. Unlike TKA, UKA knees demonstrated improved knee flexion during the gait cycle when compared to the contralateral non-operated knee. The hips also demonstrated near normal hip flexion in UKA patients. Predictably, UKA knees had significantly greater varus compared with TKA in the coronal plane. Spatiotemporal variables demonstrated similar walking speed and step length to aid a fair comparison between knee replacement groups. CONCLUSIONS: The UKA knees moved more physiologically in the sagittal plane with a greater range of motion during gait. Despite having a stiff gait pattern, the patients undergoing TKA demonstrated a more neutral alignment in the coronal plane. Neither type of knee arthroplasty restored knee kinematics to those of the non-operated side.

[Thoracoscopy in combined treatment of thymoma (in Russian only)]. / Videotorakoskopiia v kombinirovannom lechenii timom.

The experience of video-assisted thoracoscopic interventions for thymus tumors in the Research Institute of Oncology of Tomsk National Research Medical Center is presented. We also evaluate the features of postoperative management of these patients.

Mechanisms of and variables affecting UVR photoadaptation in human skin.

Humans have been exposed to solar UV radiation since their appearance on Earth and evolution has enabled most individuals to adapt to this exposure, to some degree. UV radiation produces several deleterious effects in human skin and light-skinned individuals are at greatest risk for both acute and long-term negative effects such as DNA damage, sunburn, immune suppression and skin cancer. The benefits of photoadaptation, which leads to a decreased response after acclimatization, are that humans who have skin that is capable of photoadaptation can work and play in the sun with reduced fear of painful sunburn. However, the effects of photoadaptation on DNA damage and development of skin cancer are quite complex and less well-understood. In this article, we have reviewed the current state of knowledge of UVR photoadaptation in human skin. However, more studies are needed to explore the use of UVR photoadaptation to protect against critical endpoints, such as skin cancer.

Assessing post-radiotherapy handover notes from a family physician perspective.

BACKGROUND: Across our province, post-radiotherapy (rt) handover notes are sent to family physicians (fps) after rt. Based on previous fp feedback, we created a revised post-radiotherapy handover note with more information requested by fps. The purpose of this study was to determine whether the revised handover note improved the note as a communication aid. METHODS: Potential common and rare treatment side effects, oncologist contact information, and treatment intent were added to the revised handover note. Both versions were sent alongside a questionnaire to fps. Paired t-tests were carried out to compare satisfaction differences. RESULTS: There was a response rate of 37% for the questionnaires. Significantly greater clarity in the following categories was observed: responsibility for patient follow-up (mean score improvement of 1.2 on a 7-point Likert scale, p < 0.001), follow-up schedule (1.1, p < 0.001) as well as how and when to contact the oncologist (1.4, p = 0.001). Family physicians were also more content with how the institute transitioned care back to them (1.5, p = 0.012). Overall, fps were generally satisfied with the content of the revised post-rt handover note and noted improvement over the previous version. The frequency of investigations and institute supports initiated such as counselling services were suggested further additions. CONCLUSIONS: The inclusion of potential treatment side effects, oncologist contact information, treatment intent and a well-laid out follow-up schedule were essential information needed by fps for an effective post-rt completion note. With these additions, the revised post-rt handover note showed significant improvement.

Direct oral anticoagulants: A retrospective study of bleeding, behavior, and documentation.

OBJECTIVE: To examine the effects of direct oral anticoagulants (DOACs) on bleeding complications following dental surgeries. SUBJECTS AND METHODS: This 6-year retrospective study collected data from records of patients undergoing oral surgical procedures within a university setting. An electronic health record database was searched using current procedural terminology codes for oral surgical procedures. Information regarding patient, procedural factors, and postoperative complications were extracted. Data were analyzed by Fisher's exact test. RESULTS: Of patients who had a procedural code associated with oral surgery, only 0.11% (12/11,320) took a DOAC. Twelve patients (10 males, age ranging from 44 to 90 years) underwent 17 surgeries by nine different practitioners involving 98 extractions, 14 alveoloplasties, two tuberosity reductions, and two tori removals. In nine cases, the DOAC was discontinued a mean of 52.5 hrs prior to surgery (range 12-120 hrs). Bleeding complications were not reported for patients whose drug was discontinued or continued. Documentation of drug continuation/discontinuation was poor. CONCLUSIONS: Bleeding was not observed with direct oral anticoagulation use in this oral surgery cohort. Drug discontinuation/continuation was not a factor in bleeding outcomes, and direct oral anticoagulation interruption was variable and poorly documented.

Comparison of gait kinetics in total and unicondylar knee replacement surgery.

Introduction The aim of this study was to compare kinetical data from gait analysis of patients who have undergone total and uni-condylar knee replacement. Materials and methods Thirteen patients with unilateral total knee arthroplasty (TKA) and 13 unicondylar knee arthroplasty (UKA), were included, all performed by the same surgeon more than one year prior. The Vicon gait analysis system was used. Statistical power was calculated using SPSS. Results No significant difference was found in the spatiotemporal parameters of gait and survival years of the knee prosthesis between the two groups. The UKA group was found to have significantly larger moments than the TKA group in knee adduction on the operated side and knee flexion moment on the unoperated side during the loading phase. The maximum and minimum sagittal plane moments of the operated sides in the TKA group were significantly lower than the unoperated side. The difference was most significant at pre-swing. The maximum and minimum moments on the operated sides in the UKA group were significantly lower for the knee flexion and adduction moments when compared with the unoperated side and were most prevalent during the loading phase. Conclusions These results are relevant in terms of prosthesis wear. The TKA knees had smaller magnitude moments than the UKA knees in the sagittal and coronal planes. This could explain the higher revision rates for UKA. In both groups, the non-operated knees had significantly larger moments than the operated knees, which implies that after unilateral knee replacement of either type, the non-operated knee is being put under greater stress.

Inflammatory response of disc cells against Propionibacterium acnes depends on the presence of lumbar Modic changes.

PURPOSE: Intervertebral disc with Propionibacterium acnes (P. acnes) is suggested to be an etiology of Modic type I changes in the adjacent bone marrow. However it is unknown if disc cells can respond to P. acnes and if bone marrow cells respond to bacterial and disc metabolites draining from infected discs. METHODS: Human disc cells (n = 10) were co-cultured with 10- and 100-fold excess of P. acnes over disc cells for 3 h and 24 h. Lipopolysaccharide was used as positive control. Expression of IL1, IL6, IL8, and CCL2 by disc cells was quantified by quantitative PCR. Lipase activity was measured in culture supernatants (n = 6). Human vertebral bone marrow mononuclear cells (BMNCs) (n = 2) were cultured in conditioned media from disc cell/P. acnes co-cultures and expression of IL1, IL6, IL8, and CCL2 was measured after 24 h. RESULTS: All disc cells responded to lipopolysaccharide but only 6/10 responded to P. acnes with increased cytokine expression. Cytokine increase was time- but not P. acnes concentration-dependent. Disc cell responsiveness was associated with the presence of lumbar Modic changes in the donor. Lipase activity was increased independent of disc cell responsiveness. BMNCs responded with inflammatory activity only when cultured in supernatants from responsive disc cell lines. CONCLUSION: Disc cell responsiveness to P. acnes associates with the presence of lumbar Modic changes. Furthermore, bone marrow cells had an inflammatory response to the cocktail of disc cytokines and P. acnes metabolites. These data indicate that low virulent P. acnes infection of the disc is a potential exacerbating factor to Modic changes.

Description of a method for inducing fetal growth restriction in the spiny mouse.

Intrauterine or fetal growth restriction (IUGR) is a major complication of pregnancy and leads to significant perinatal morbidities and mortality. Typically, induction of IUGR in animals involves the complete occlusion or ablation of vessels to the uterus or placenta, acutely impairing blood flow and fetal growth, usually with high fetal loss. We aimed to produce a model of reduced fetal growth in the spiny mouse with minimal fetal loss. At 27 days gestational age (term is 38-39 days), a piece of silastic tubing was placed around the left uterine artery to prevent the further increase of uterine blood flow with advancing gestation to induce IUGR (occluded). Controls were generated from sham surgeries without placement of the tubing. Dams were humanely euthanized at 37 days gestational age and all fetuses and placentas were weighed and collected. Of the 17 dams that underwent surgery, 15 carried their pregnancies to 37 days gestational age and 95% of fetuses survived to this time. The difference in fetal body weight between occluded and control was ~21% for fetuses in the left uterus side: there were no differences for fetuses in the right uterus side. Offspring from the occluded group had significantly lower brain, liver, lung, kidney and carcass weights compared with shams. Preventing the gestation-related increase of uterine blood flow induced significant growth restriction in the fetal spiny mouse, with minimal fetal loss. This technique could be readily adapted for other small animal.

Expression of DNA damage response proteins in cervical cancer patients treated with radical chemoradiotherapy.

OBJECTIVE: The management of locally advanced cervical cancer has improved significantly with the advent of cisplatin-based chemoradiotherapy (CRT) as the primary treatment regimen. Nevertheless, a significant proportion of patients fail to respond or relapse on this treatment and have a very poor prognosis. Our goal was to determine the prognostic value of a panel of proteins involved in detection and repair of DNA damage. METHODS: We performed fluorescence immunohistochemistry, and used software analysis to assess expression of DNA damage response proteins ATM, DNA-PKcs, PARP-1, Ku70 and Ku86 in 117 pre-treatment specimens from patients with locally advanced cervical cancer. We compared expression to clinicopathologic correlates to determine prognostic significance. RESULTS: Five-year progression-free survival was significantly lower in the low expressors than in high expressors of ATM (35% vs. 58%, p=0.044) and PARP-1 (24% vs. 61%, p=0.003), and showed a trend to significance for DNA-PKcs (30% vs. 60%, p=0.050). Low expression of the same proteins also correlated significantly with lower overall survival. In multivariable analysis, adjusted for FIGO stage and tumor size, low ATM and PARP-1 expression was significantly associated with both poorer progression-free and overall survival. Pairwise analyses indicated that expression levels of these proteins were correlated. CONCLUSIONS: Expression of DNA damage response proteins in cervical cancer is associated with outcome in patients treated with CRT. Immunohistochemical analysis of these proteins may be useful in guiding treatment decisions in such patients.

The MAYAK WORKER DOSIMETRY SYSTEM (MWDS-2013): ESTIMATION OF PLUTONIUM SKELETAL BURDEN FROM LIMITED AUTOPSY BONE SAMPLES FROM MAYAK PA WORKERS.

The method to estimate total skeleton plutonium burden of former Mayak Production Association (MPA) workers from limited bone samples obtained at autopsy is described. From two to nine bone samples were obtained at autopsies conducted from the mid-1950s to 2013. Plutonium was measured using alpha-radiometry up to 2000 and later by alpha-spectrometry. The method was validated using data from whole-body donations from the United States Transuranium and Uranium Registries (USTUR). The developed algorithm overestimated the USTUR values from 20 to 40%, that is quite acceptable for conservative estimation. Late-in-life liver diseases known to redistribute plutonium between liver and skeleton were not associated with significant differences in plutonium deposition among sampled bones, except for the pelvis. Sources of uncertainties are discussed and future studies will address the reduction of these uncertainties. This algorithm can be used to obtain data in support of the development of biokinetic, dosimetric and risk models for humans exposed to plutonium.

Awareness of occupational skin disease in the service sector.

BACKGROUND: Occupational skin disease (OSD) is a common occupational disease. Although primary prevention strategies are known, OSDs remain prevalent in a variety of work environments including the service sector (restaurant/food services, retail/wholesale, tourism/hospitality and vehicle sales and service). AIMS: To obtain information about awareness and prevention of OSD in the service sector. METHODS: Focus groups and a survey were conducted with two groups. The first consisted of staff of the provincial health and safety association for the service sector and the second group comprised representatives from sector employers. Focus groups highlighted key issues to inform the survey that obtained information about perceptions of awareness and prevention of OSD and barriers to awareness and prevention. RESULTS: Both provincial health and safety association staff and sector employer representatives highlighted low awareness and a low level of knowledge of OSD in the sector. Barriers to awareness and prevention included a low reported incidence of OSD, low priority, lack of training materials, lack of time and cost of training, lack of management support and workplace culture. CONCLUSIONS: A starting point for improving prevention of OSD in the service sector is increased awareness. Identification of the barriers to awareness and prevention will help to shape an awareness campaign and prevention strategies. Building on existing experience in Europe will be important.