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Abstract Background and purpose Radiotherapy (RT) is an essential treatment modality against cancer and becoming even more in demand due to the anticipated increase in cancer incidence. Due to the rapid development of RT technologies amid financial challenges, we aimed to assess the available RT facilities and the issues with achieving health equity based on current equipment compared to the previous reports from Iran. Materials and methods A survey arranged by the Iran Cancer Institute's Radiation Oncology Research Center (RORC) was sent to all of the country's radiotherapy centers in 2022. Four components were retrieved: the reimbursement type, equipment, human resources, and patient load. To calculate the radiotherapy utilization rate (RUR), the Lancet Commission was used. The findings were compared with the previous national data. Results Seventy-six active radiotherapy centers with 123 Linear accelerators (LINACs) were identified. The centers have been directed in three ways. 10 (20 LINACs), 36 (50 LINACs), and 30 centers (53 LINACs) were charity-, private-, and public-based, respectively. Four provinces had no centers. There was no active intraoperative radiotherapy machine despite its availability in 4 centers. One orthovoltage X-ray machine was active and 14 brachytherapy devices were treating patients. There were 344, 252, and 419 active radiation oncologists, medical physicists, and radiation therapy technologists, respectively. The ratio of LINAC and radiation oncologists to one million populations was 1.68 and 4.10, respectively. Since 2017, 35±5 radiation oncology residents have been trained each year. Conclusion There has been a notable growth in RT facilities since the previous reports and Iran's situation is currently acceptable among LMICs. However, there is an urgent need to improve the distribution of the RT infrastructure and provide more facilities that can deliver advanced techniques.

Abstract Background Centrally located lung tumors present treatment challenges given their proximity to mediastinal structures including the central airway, esophagus, major vessels, and heart. Therapeutic options can be limited for medically inoperable patients, particularly if they have received previous thoracic radiotherapy. High dose rate (HDR) brachyablation was developed to improve the therapeutic ratio for patients with central lung tumors. The purpose of this study is to report initial safety and efficacy outcomes with this treatment for central lung malignancies. Methods From September 2015 to August 2019, a total of 25 patients with 37 pulmonary tumors were treated with percutaneous HDR brachyablation. Treatment was delivered by a multi-disciplinary team of interventional radiologists, pulmonologists, and radiation oncologists. Twenty-three patients received a median dose of 21.5 Gy (range 15–27.5) in a single fraction, whereas two patients received median dose of 24.75 Gy (range 24–25.5) over 2–3 fractions. Tumor local control (LC) was evaluated by Response Evaluation Criteria in Solid Tumors v1.1. Treatment-related toxicities were graded by Common Terminology Criteria for Adverse Events v5.0, with adverse events less than 90 days defined as acute, and those occurring later were defined as late. LC, progression-free survival (PFS), and overall survival (OS) rates were estimated by the Kaplan–Meier method. Results Of 37 treated tumors, 88% were metastatic. Tumor location was central and ultra-central in 24.3% and 54.1%, respectively. Average tumor volume was 11.6 cm3 (SD 12.4, range 0.57–62.8). Median follow-up was 19 months (range 3–48). Two–year LC, PFS, and OS were 96.2%, 29.7%, and 65.5%, respectively. Thirteen of 39 (33.3%) catheter implantation procedures were associated with trace minor pneumothorax requiring no intervention, 1 (2.5%) procedure with minor radiographic pulmonary hemorrhage, and 4 (10.3%) with major pneumothorax requiring chest tube insertions. All procedural complications resolved within 24 h from treatment. Acute grade 1–2 toxicity was identified in 4 patients, whereas none developed late toxicity beyond 90 days of follow-up. Conclusion Percutaneous HDR brachyablation is a safe and promising treatment option for centrally located primary and metastatic lung tumors. Future comparisons with stereotactic body radiotherapy and other ablative techniques are warranted to expand multi-disciplinary management options.

Abstract Background Retrotransposons have been extensively studied in plants and animals and have been shown to have an impact on human genome dynamics and evolution. Their ability to move within genomes gives retrotransposons to affect genome instability. Methods we examined the polymorphic inserted AluYa5, evolutionary young Alu, in the progesterone receptor gene to determine the effects of Alu insertion on molecular environment. We used mono-allelic inserted cell lines which carry both Alu-present and Alu-absent alleles. To determine the epigenetic change and gene expression, we performed restriction enzyme digestion, Pyrosequencing, and Chromatin Immunoprecipitation. Results We observed that the polymorphic insertion of evolutionally young Alu causes increasing levels of DNA methylation in the surrounding genomic area and generates inactive histone tail modifications. Consequently the Alu insertion deleteriously inactivates the neighboring gene expression. Conclusion The mono-allelic Alu insertion cell line clearly showed that polymorphic inserted repetitive elements cause the inactivation of neighboring gene expression, bringing aberrant epigenetic changes.

Abstract Introduction Though animal-related injuries and fatalities have been documented throughout the world, the variety of attacks by wild animals native to rural East Africa are less commonly described. Given the proximity of our northwestern Tanzania hospital to Lake Victoria, Lake Tanganyika, and the Serengeti National Park, and presentation of several patients attacked by bush animals and suffering a variety of complex injuries, we sought to report the pattern of attacks and surgical management in a resource-limited setting. Materials and methods Four patients who were admitted to the northwestern Tanzania tertiary referral hospital, Bugando Medical Centre (BMC), in 2010-2011 suffered attacks by different bush animals: hyena, elephant, crocodile, and vervet monkey. These patients were triaged as trauma patients in the Casualty Ward, then admitted for inpatient monitoring and treatment. Their outcomes were followed to discharge. Results The age and gender of the patients attacked was variable, though all but the pediatric patient were participating in food gathering or guarding activities in rural locations at the time of the attacks. All patients required surgical management of their injuries, which included debridement and closure of wounds, chest tube insertion, amputation, and external fixation of an extremity fracture. All patients survived and were discharged home. Discussion Though human injuries secondary to encounters with undomesticated animals such as cows, moose, and camel are reported, they often are indirect traumas resulting from road traffic collisions. Snake attacks are well documented and common. However, this series of unique bush animal attacks describes the initial and surgical management of human injuries in the resource-limited setting of the developing world. Conclusion Animal attacks are common throughout the world, but their pattern may vary in Africa throughout jungle and bush environmental settings. It is important to understand the management of these attacks in resource-limited health care environment. Further, the growing population and human encroachment on previously wild habitats such as the northwestern Tanzania bush argues for increased community awareness to assist in prevention of human injuries by animals.

Abstract Background The physiological responses to hypoxaemia and cellular hypoxia are poorly understood, and inter-individual differences in performance at altitude and outcome in critical illness remain unexplained. We propose a model for exploring adaptation to hypoxia in the critically ill: the study of healthy humans, progressively exposed to environmental hypobaric hypoxia (EHH). The aim of this study was to describe the spectrum of adaptive responses in humans exposed to graded EHH and identify factors (physiological and genetic) associated with inter-individual variation in these responses. Methods Design Observational cohort study of progressive incremental exposure to EHH. Setting University human physiology laboratory in London, UK (75 m) and 7 field laboratories in Nepal at 1300 m, 3500 m, 4250 m, 5300 m, 6400 m, 7950 m and 8400 m. Participants 198 healthy volunteers and 24 investigators trekking to Everest Base Camp (EBC) (5300 m). A subgroup of 14 investigators studied at altitudes up to 8400 m on Everest. Main outcome measures Exercise capacity, exercise efficiency and economy, brain and muscle Near Infrared Spectroscopy, plasma biomarkers (including markers of inflammation), allele frequencies of known or suspected hypoxia responsive genes, spirometry, neurocognitive testing, retinal imaging, pupilometry. In nested subgroups: microcirculatory imaging, muscle biopsies with proteomic and transcriptomic tissue analysis, continuous cardiac output measurement, arterial blood gas measurement, trans-cranial Doppler, gastrointestinal tonometry, thromboelastography and ocular saccadometry. Results Of 198 healthy volunteers leaving Kathmandu, 190 reached EBC (5300 m). All 24 investigators reached EBC. The completion rate for planned testing was more than 99% in the investigator group and more than 95% in the trekkers. Unique measurements were safely performed at extreme altitude, including the highest (altitude) field measurements of exercise capacity, cerebral blood flow velocity and microvascular blood flow at 7950 m and arterial blood gas measurement at 8400 m. Conclusions This study demonstrates the feasibility and safety of conducting a large healthy volunteer cohort study of human adaptation to hypoxia in this difficult environment. Systematic measurements of a large set of variables were achieved in 222 subjects and at altitudes up to 8400 m. The resulting dataset is a unique resource for the study of genotype:phenotype interactions in relation to hypoxic adaptation.

Abstract Background Prolonged exposure to war has severely impacted the provision of health services in the Democratic Republic of the Congo (DRC). Health infrastructure has been destroyed, health workers have fled and government support to health care services has been made difficult by ongoing conflict. Poor reproductive health (RH) indicators illustrate the effect that the prolonged crisis in DRC has had on the on the reproductive health (RH) of Congolese women. In 2007, with support from the RAISE Initiative, the International Rescue Committee (IRC) and CARE conducted baseline assessments of public hospitals to evaluate their capacities to meet the RH needs of the local populations and to determine availability, utilization and quality of RH services including emergency obstetric care (EmOC) and family planning (FP). Methods Data were collected from facility assessments at nine general referral hospitals in five provinces in the DRC during March, April and November 2007. Interviews, observation and clinical record review were used to assess the general infrastructure, EmOC and FP services provided, and the infection prevention environment in each of the facilities. Results None of the nine hospitals met the criteria for classification as an EmOC facility (either basic or comprehensive). Most facilities lacked any FP services. Shortage of trained staff, essential supplies and medicines and poor infection prevention practices were consistently documented. All facilities had poor systems for routine monitoring of RH services, especially with regard to EmOC. Conclusions Women's lives can be saved and their well-being improved with functioning RH services. As the DRC stabilizes, IRC and CARE in partnership with the local Ministry of Health and other service provision partners are improving RH services by: 1) providing necessary equipment and renovations to health facilities; 2) improving supply management systems; 3) providing comprehensive competency-based training for health providers in RH and infection prevention; 4) improving referral systems to the hospitals; 5) advocating for changes in national RH policies and protocols; and 6) providing technical assistance for monitoring and evaluation of key RH indicators. Together, these initiatives will improve the quality and accessibility of RH services in the DRC - services which are urgently needed and to which Congolese women are entitled by international human rights law.