Virilization at puberty in adolescent girls may reveal a 46,XY disorder of sexual development.

Although hyperandrogenism is a frequent cause of consultation in adolescent girls, more severe forms with virilization must lead to suspicion of an adrenal or ovarian tumor. However, they may also reveal a 46,XY disorder of sexual development (DSD). Here, we describe four adolescent girls referred for pubertal virilization and in whom we diagnosed a 46,XY DSD. We performed gene mutation screening by Sanger sequencing (all patients) and by next-generation sequencing (NGS) in patient #4. We identified new heterozygous NR5A1 gene variants in patients #1 and #2 and a homozygous SRD5A2 gene deletion in patient #3. Patient #4 received a diagnosis of complete androgen insensitivity in childhood; however, due the unusual pubertal virilization, we completed the gene analysis by NGS that revealed two heterozygous HSD17B3 variants. This work underlines the importance of considering the hypothesis of 46,XY DSD in adolescent girls with unexplained virilization at puberty.

COVID-19-mediated patient delay caused increased total ischaemic time in ST-segment elevation myocardial infarction.

BACKGROUND: The current study aimed to evaluate changes in treatment delay and outcome for ST-segment elevation myocardial infarction (STEMI) in the Netherlands during the first coronavirus disease 2019 (COVID-19) outbreak, thereby comparing regions with a high and low COVID-19 hospitalisation rate. METHODS: Clinical characteristics, STEMI timing variables, 30-day all-cause mortality and cardiovascular complications of all consecutive patients admitted for STEMI from 1 January to 30 June in 2020 and 2019 to six hospitals performing a high volume of percutaneous coronary interventions were collected retrospectively using data from the Netherlands Heart Registry, hospital records and ambulance report forms. Patient delay, pre-hospital delay and door-to-balloon time before and after the outbreak of COVID-19 were compared to the equivalent periods in 2019. RESULTS: A total of 2169 patients were included. During the outbreak median total treatment delay significantly increased (2 h 51 min vs 2 h 32 min; p = 0.043) due to an increased patient delay (1 h 20 min vs 1 h; p = 0.030) with more late presentations > 24 h (1.1% vs 0.3%) in 2020. This increase was particularly evident during the peak phase of COVID-19 in regions with a high COVID-19 hospitalisation rate. During the peak phase door-to-balloon time was shorter (38 min vs 43 min; p = 0.042) than in 2019. All-cause 30-day mortality was comparable in both time frames (7.8% vs 7.3%; p = 0.797). CONCLUSIONS: During the outbreak of COVID-19 patient delay caused an increase in total ischaemic time for STEMI, with a more pronounced delay in high-endemic regions, stressing the importance of good patient education during comparable crisis situations.

[Environmental endocrine disruptors and fertility]. / Perturbateurs endocriniens environnementaux et fertilité.

Endocrine disruptor chemicals (EDCs) are ubiquitous contaminants in the environment, wildlife, and humans. During the last 20 years, several epidemiological, clinical and experimental studies have demonstrated the role of EDCs on the reduction of male and female fertility. The concept of foetal origins of adult disease is particularly topical in the field of reproduction. Moreover, exposure to EDCs during pregnancy has been shown to influence epigenetic programming of endocrine signalling and other important physiological pathways, and provided the basis for multi- and transgenerational transmission of adult diseases. However, the large panel of EDCs simultaneously present in the air, sol and water makes the quantification of human exposition still a challenge. Gas chromatography coupled with mass spectrometry, the measurement of total plasmatic hormonal bioactivity on stably transfected cell lines as well as the EDC analysis in hair samples are useful methods of evaluation. More recently, microRNAs analysis offers a new perspective in the comprehension of the mechanisms behind the modulation of cellular response to foetal or post-natal exposure to EDCs. They will help researchers and clinicians in identifying EDCs exposition markers and new therapeutic approaches in the future.

Comportamiento meteorológico durante la sequía de medio verano en Guatemala / Meteorological behavior during the mid-summer drought in Guatemala

El objetivo de esta investigación consistió en explorar el comportamiento histórico de la temperatura, precipitación y la radiación saliente de onda larga (OLR) para Guatemala, durante el período de sequía de medio verano (canícula). El procedimiento metodológico partió del uso de la base de datos de 38 estaciones meteorológicas del Instituto Nacional de Sismología, Vulcanología, Meteorología e Hidrología, de Guatemala (Insivumeh), del periodo de 1971-2019. Se realizaron promedios para cada región del país; Norte, Caribe, Franja Trasversal, Pacífico, Boca Costa, Oriente y Altiplano. Mediante series de tiempo con resolución temporal diaria, se evaluaron señales de cambio y se hicieron gráficas de OLR con la base de datos del Centro Nacional de Predicción Ambiental (NCEP, por sus siglas en inglés) de 2.5° x 2.5° de resolución. Los resultados muestran que la temperatura ha aumentado en dicho periodo, encontrando que en algunas regiones climáticas el aumento ha sido de 1 ºC y en otras de 2 ºC. Asimismo, se encontró que los días sin lluvia tienen una tendencia hacia el aumento, al igual que la radiación saliente de onda larga. La canícula, es un fenómeno meteorológico que está siendo afectado por el cambio climático, y en la medida que se siga experimentando un calentamiento diferencial entre los océanos Pacífico y Atlántico, influirá en el cambio de clima para Guatemala. En conclusión, durante la canícula se manifestaron señales de tendencia hacia el aumento de la temperatura, aumento de días sin lluvia y aumento de OLR.

The objective of this research was to explore the historical behavior of temperature, precipitation and outgoing longwave radiation (OLR) for Guatemala, during the midsummer drought period (canícula). The methodological procedure was based on the use of the database of 38 stations of the National Institute of Seismology, Volcanology, Meteorology and Hydrology, of Guatemala (Insivumeh), from the period 1971-2019. Averages were made for each region of the country; North, Caribbean, Transversal Strip, Pacific, Boca Costa, East and Altiplano. Using time series with daily temporal resolution, signals of change were evaluated and OLR plots were made using the National Center for Environmental Prediction (NCEP) database at 2.5° x 2.5° resolution. The results show that the temperature has reached in this period, finding that in some climatic regions the increase has been 1 ºC and in others 2 ºC. Likewise, it was found that the days without rain have a tendency to increase, as well as the outstanding longwave radiation. The heat wave is a meteorological phenomenon that is being affected by climate change, and to the extent that differential heating between the Pacific and Atlantic oceans continues to be experienced, it will influence the climate change for Guatemala. In conclusion, during the heat wave there are signs of a trend towards an increase in temperature, an increase in days without rain and an increase in OLR,

Framework Implementation of the INSPIRE ICOPE-CARE Program in Collaboration with the World Health Organization (WHO) in the Occitania Region.

INTRODUCTION: Limiting the number of dependent older people in coming years will be a major economic and human challenge. In response, the World Health Organization (WHO) has developed the «Integrated Care for Older People (ICOPE)¼ approach. The aim of the ICOPE program is to enable as many people as possible to age in good health. To reach this objective, the WHO proposes to follow the trajectory of an individual's intrinsic capacity, which is the composite of all their physical and mental capacities and comprised of multiple domains including mobility, cognition, vitality / nutrition, psychological state, vision, hearing. OBJECTIVE: The main objective of the INSPIRE ICOPE-CARE program is to implement, in clinical practice at a large scale, the WHO ICOPE program in the Occitania region, in France, to promote healthy aging and maintain the autonomy of seniors using digital medicine. METHOD: The target population is independent seniors aged 60 years and over. To follow this population, the 6 domains of intrinsic capacity are systematically monitored with pre-established tools proposed by WHO especially STEP 1 which has been adapted in digital form to make remote and large-scale monitoring possible. Two tools were developed: the ICOPE MONITOR, an application, and the BOTFRAIL, a conversational robot. Both are connected to the Gerontopole frailty database. STEP 1 is performed every 4-6 months by professionals or seniors themselves. If a deterioration in one or more domains of intrinsic capacity is identified, an alert is generated by an algorithm which allows health professionals to quickly intervene. The operational implementation of the INSPIRE ICOPE-CARE program in Occitania is done by the network of Territorial Teams of Aging and Prevention of Dependency (ETVPD) which have more than 2,200 members composed of professionals in the medical, medico-social and social sectors. Targeted actions have started to deploy the use of STEP 1 by healthcare professionals (physicians, nurses, pharmacists,…) or different institutions like French National old age insurance fund (CNAV), complementary pension funds (CEDIP), Departmental Council of Haute Garonne, etc. Perspective: The INSPIRE ICOPE-CARE program draws significantly on numeric tools, e-health and digital medicine to facilitate communication and coordination between professionals and seniors. It seeks to screen and monitor 200,000 older people in Occitania region within 3 to 5 years and promote preventive actions. The French Presidential Plan Grand Age aims to largely implement the WHO ICOPE program in France following the experience of the INSPIRE ICOPE-CARE program in Occitania.

Infiltración neoplásica cutánea por un linfoma linfoplasmocítico en una paciente con macroglobulinemia de Waldenström / Neoplastic Cutaneous Infiltration by Lymphoplasmacytic Lymphoma in a Patient with Waldenström's Macroglobulinemia

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Testotoxicosis without Testicular Mass: Revealed by Peripheral Precocious Puberty and Confirmed by Somatic LHCGR Gene Mutation.

Purpose: Testotoxicosis is an autosomal dominant form of limited gonadotropin-independent precocious puberty in boys. It is caused by a heterozygous constitutively activating mutation of the LHCGR gene encoding the luteinizing/hormone receptor (LHR). Some twenty mutations of the LHCGR gene have been reported. Most of them are constitutive mutations isolated from blood leukocyte DNA, although others are somatic, found only in testicular tumoural tissue. In all the previously reported cases of these somatic mutations, the tumour, whether a nodular Leydig cell adenoma or hyperplasia, was easily visible on testicular ultrasonography. The aim of this study was to describe an unusual presentation of a patient with the clinical and hormonal characteristics of testotoxicosis but no well-circumscribed lesion at testicular ultrasonography.Materials and Methods: Molecular analysis of the LHCGR gene was performed by direct sequencing of DNA extracted from peripheral leucocytes and testicular biopsy.Results: Molecular analysis didn't find any LHR mutation in blood, whereas it revealed for the first time a somatic D578H mutation in testicular tissue despite no evidence of a nodular aspect at testis ultrasonography.Conclusions: This observation underlines the need to look for a somatic LHCGR gene mutation from the testicular biopsies of all boys with testotoxicosis with no constitutive LHCGR gene mutation identified from blood DNA, even in the absence of circumscribed testicular lesion at ultrasonography. In addition, based on the known link between LHR mutations and testicular tumourigenesis, yearly ultrasound monitoring of the testes should be considered for these patients.

The conserved C-terminus of Sss1p is required to maintain the endoplasmic reticulum permeability barrier.

The endoplasmic reticulum (ER) is the entry point to the secretory pathway and major site of protein biogenesis. Translocation of secretory and integral membrane proteins across or into the ER membrane occurs via the evolutionarily conserved Sec61 complex, a heterotrimeric channel that comprises the Sec61p/Sec61α, Sss1p/Sec61γ, and Sbh1p/Sec61ß subunits. In addition to forming a protein-conducting channel, the Sec61 complex also functions to maintain the ER permeability barrier, preventing the mass free flow of essential ER-enriched molecules and ions. Loss in Sec61 integrity is detrimental and implicated in the progression of disease. The Sss1p/Sec61γ C terminus is juxtaposed to the key gating module of Sec61p/Sec61α, and we hypothesize it is important for gating the ER translocon. The ER stress response was found to be constitutively induced in two temperature-sensitive sss1 mutants (sss1ts ) that are still proficient to conduct ER translocation. A screen to identify intergenic mutations that allow for sss1ts cells to grow at 37 °C suggests the ER permeability barrier to be compromised in these mutants. We propose the extreme C terminus of Sss1p/Sec61γ is an essential component of the gating module of the ER translocase and is required to maintain the ER permeability barrier.

A new tissue segmentation method to calculate 3D dose in small animal radiation therapy.

BACKGROUND: In pre-clinical animal experiments, radiation delivery is usually delivered with kV photon beams, in contrast to the MV beams used in clinical irradiation, because of the small size of the animals. At this medium energy range, however, the contribution of the photoelectric effect to absorbed dose is significant. Accurate dose calculation therefore requires a more detailed tissue definition because both density (ρ) and elemental composition (Zeff) affect the dose distribution. Moreover, when applied to cone beam CT (CBCT) acquisitions, the stoichiometric calibration of HU becomes inefficient as it is designed for highly collimated fan beam CT acquisitions. In this study, we propose an automatic tissue segmentation method of CBCT imaging that assigns both density (ρ) and elemental composition (Zeff) in small animal dose calculation. METHODS: The method is based on the relationship found between CBCT number and ρ*Zeff product computed from known materials. Monte Carlo calculations were performed to evaluate the impact of ρZeff variation on the absorbed dose in tissues. These results led to the creation of a tissue database composed of artificial tissues interpolated from tissue values published by the ICRU. The ρZeff method was validated by measuring transmitted doses through tissue substitute cylinders and a mouse with EBT3 film. Measurements were compared to the results of the Monte Carlo calculations. RESULTS: The study of the impact of ρZeff variation over the range of materials, from ρZeff = 2 g.cm- 3 (lung) to 27 g.cm- 3 (cortical bone) led to the creation of 125 artificial tissues. For tissue substitute cylinders, the use of ρZeff method led to maximal and average relative differences between the Monte Carlo results and the EBT3 measurements of 3.6% and 1.6%. Equivalent comparison for the mouse gave maximal and average relative differences of 4.4% and 1.2%, inside the 80% isodose area. Gamma analysis led to a 94.9% success rate in the 10% isodose area with 4% and 0.3 mm criteria in dose and distance. CONCLUSIONS: Our new tissue segmentation method was developed for 40kVp CBCT images. Both density and elemental composition are assigned to each voxel by using a relationship between HU and the product ρZeff. The method, validated by comparing measurements and calculations, enables more accurate small animal dose distribution calculated on low energy CBCT images.

Neuroblastoma chemotherapy can be augmented by immunotargeting O-acetyl-GD2 tumor-associated ganglioside.

Despite recent advances in high-risk neuroblastoma therapy, the prognosis for patients remains poor. In addition, many patients suffer from complications related to available therapies that are highly detrimental to their quality of life. New treatment modalities are, thus, urgently needed to further improve the efficacy and reduce the toxicity of existing therapies. Since antibodies specific for O-acetyl GD2 ganglioside display pro-apoptotic activity against neuroblastoma cells, we hypothesized that combination of immunotherapy could enhance tumor efficacy of neuroblastoma chemotherapy. We demonstrate here that combination of anti-O-acetyl GD2 monoclonal antibody 8B6 with topotecan synergistically inhibited neuroblastoma cell proliferation, as shown by the combination index values. Mechanistically, we evidence that mAb 8B6 induced plasma cell membrane lesions, consistent with oncosis. Neuroblastoma tumour cells treated with mAb 8B6 indeed showed an increased uptake of topotecan by the tumor cells and a more profound tumor cell death evidenced by increased caspase-3 activation. We also found that the combination with topotecan plus monoclonal antibody 8B6 showed a more potent anti-tumor efficacy in vivo than either agent alone. Importantly, we used low-doses of topotecan with no noticeable side effect. Our data suggest that chemo-immunotherapy combinations may improve the clinical efficacy and safety profile of current chemotherapeutic modalities of neuroblastoma.

[Intensive training and menstrual disorders in young female: Impact on bone mass]. / Sport intensif et troubles du cycle chez la jeune femme : retentissement sur la masse osseus.

Participation in recreational physical activity is widely acknowledged to provide significant health benefits. Conversely, intense training imposes several constraints, such as intermittent or chronic metabolic and psychogenic training stressors and maintenance of very low body fat to maximize performance. Adolescent and adult athletic women are therefore at risk of overtraining and/or poor dietary intake, which may have several consequences for endocrine function particularly on hypothalamic-pituitary-gonadal axis. Female athletes, particularly those participating in sports needing leanness or low body weight, present a high prevalence of menstrual disorders with clinical manifestations ranging from delayed menarche, oligomenorrhea to primary and secondary amenorrhea. A high degree of variability according to the type of sport and the intensity of the practice is however observed. Exercise-related reproductive dysfunction may have some consequences for growth velocity and peak bone mass acquisition during adolescence and bone pathologies in adults. Recent findings highlight the endocrine role of adipose tissue and energy balance in the regulation of homeostasis and reproductive function. A better understanding of the mechanisms whereby intense training affects the endocrine systems may orient research to develop innovative strategies probably based on individualized nutritional approach to improve the medical care of these female athletes and protect their reproductive function.

Validation of fast Monte Carlo dose calculation in small animal radiotherapy with EBT3 radiochromic films.

In preclinical studies, the absorbed dose calculation accuracy in small animals is fundamental to reliably investigate and understand observed biological effects. This work investigated the use of the split exponential track length estimator (seTLE), a new kerma based Monte Carlo dose calculation method for preclinical radiotherapy using a small animal precision micro irradiator, the X-RAD 225Cx. Monte Carlo modelling of the irradiator with GATE/GEANT4 was extensively evaluated by comparing measurements and simulations for half-value layer, percent depth dose, off-axis profiles and output factors in water and water-equivalent material for seven circular fields, from 20 mm down to 1 mm in diameter. Simulated and measured dose distributions in cylinders of water obtained for a 360° arc were also compared using dose, distance-to-agreement and gamma-index maps. Simulations and measurements agreed within 3% for all static beam configurations, with uncertainties estimated to 1% for the simulation and 3% for the measurements. Distance-to-agreement accuracy was better to 0.14 mm. For the arc irradiations, gamma-index maps of 2D dose distributions showed that the success rate was higher than 98%, except for the 0.1 cm collimator (92%). Using the seTLE method, MC simulations compute 3D dose distributions within minutes for realistic beam configurations with a clinically acceptable accuracy for beam diameter as small as 1 mm.

Endocrine and molecular investigations in a cohort of 25 adolescent males with prominent/persistent pubertal gynecomastia.

Pubertal gynecomastia is a common condition observed in up to 65% of adolescent males. It is usually idiopathic and tends to regress within 1-2 years. In this descriptive cross-sectional study, we investigated 25 adolescent males with prominent (>B3) and/or persistent (>2 years) pubertal gynecomastia (P/PPG) to determine whether a hormonal/genetic defect might underline this condition. Endocrine investigation revealed the absence of hormonal disturbance for 18 boys (72%). Three patients presented Klinefelter syndrome and three a partial androgen insensitivity syndrome (PAIS) as a result of p.Ala646Asp and p.Ala45Gly mutations of the androgen receptor gene. The last patient showed a 17α-hydroxylase/17,20-lyase deficiency as a result of a compound heterozygous mutation of the CYP17A1 gene leading to p.Pro35Thr(P35T) and p.Arg239Stop(R239X) in the P450c17 protein. Enzymatic activity was analyzed: the mutant protein bearing the premature stop codon R239X showed a complete loss of 17α-hydroxylase and 17,20-lyase activity. The mutant P35T seemed to retain 15-20% of 17α-hydroxylase and about 8-10% of 17,20-lyase activity. This work demonstrates that P/PPG had an endocrine/genetic cause in 28% of our cases. PAIS may be expressed only by isolated gynecomastia as well as by 17α-hydroxylase/17,20-lyase deficiency. Isolated P/PPG is not always a 'physiological' condition and should thus be investigated through adequate endocrine and genetic investigations, even though larger studies are needed to better determine the real prevalence of genetic defects in such patients.

Evidence of a link between resting energy expenditure and bone remodelling, glucose homeostasis and adipokine variations in adolescent girls with anorexia nervosa.

UNLABELLED: Low bone mass is a consequence of anorexia nervosa (AN). This study assessed the effects of energy deficiency on various bone and hormonal parameters. The interrelationships between energy deficiency and bone remodelling, glucose homeostasis and adipokines underscore the importance of preventing energy deficiency to limit demineralisation and hormonal alterations in AN patients. INTRODUCTION: Low areal bone mineral density (aBMD) is a well-known consequence of AN. However, the impact of reduced energy expenditure on bone metabolism is unknown. This study assessed the effects of energy deficiency on bone remodelling and its potential interactions with glucose homeostasis and adipose tissue-derived hormones in AN, a clinical model for reduced energy expenditure. METHODS: Fifty women with AN and 50 age-matched controls (mean age 18.1 ± 2.7 and 18.0 ± 2.1 years, respectively) were enrolled. aBMD was determined with DXA. Resting energy expenditure (REEm), a marker of energy status, was indirectly assessed by calorimetry. Bone turnover markers, undercarboxylated osteocalcin (ucOC), parameters of glucose homeostasis, adipokines and growth factors were concomitantly evaluated. RESULTS: AN patients presented low aBMD at all bone sites. REEm, bone formation markers, ucOC, glucose, insulin, HOMA-IR, leptin and IGF-1 were significantly reduced, whereas the bone resorption marker, leptin receptor (sOB-R) and adiponectin were elevated in AN compared with CON. In AN patients, REEm was positively correlated with weight, BMI, whole body (WB) fat mass, WB fat-free soft tissue, markers of bone formation, glucose, insulin, HOMA-IR, leptin and IGF-1 and negatively correlated with the bone resorption marker and sOB-R. Biological parameters, aBMD excepted, appeared more affected by the weight variation in the last 6 months than by the disease duration. CONCLUSIONS: The strong interrelationships between REEm and bone remodelling, glucose homeostasis and adipokines underscore the importance of preventing energy deficiency to limit short- and long-term bone demineralisation and hormonal alterations in AN patients.

[McCune-Albright syndrome revealed by Blaschko-linear café-au-lait spots on the back]. / Syndrome de McCune-Albright révélé par des taches café-au-lait blaschko-linéaires du dos.

BACKGROUND: McCune-Albright syndrome is a rare sporadic disease defined by the triad of café-au-lait spots, fibrous dysplasia of bone and endocrine disorder. Diagnosis is classically confirmed by the presence of bone lesions or precocious puberty. We report a case of McCune-Albright syndrome diagnosed solely on the basis of the cutaneous signs. PATIENTS AND METHODS: A four-year-old girl was seen in our clinic due to the presence of congenital café-au-lait spots on her back. These macules were irregular, with jagged borders, and were disposed in a broad band on the left shoulder and in the lumbar region, in a Blaschko-linear pattern. McCune-Albright syndrome was immediately suspected, despite the absence of other signs of the disease. Genetic assessment carried out a year and a half later confirmed the diagnosis, with arginine substitution at position 201 of Gs alpha protein. The child was still asymptomatic. Regular radiographic and endocrine assessments remained normal for three years until the sudden appearance at the age of seven years of precocious puberty and radiographic evidence of fibrous dysplasia of the right hand. DISCUSSION: Café-au-lait spots are very common in the general population. An underlying genetic disorder should only be sought when such spots are multiple. However, in the case of McCune-Albright syndrome, it is the irregular borders and the Blaschko-linear arrangement of the spots in broad irregular bands that are pathognomonic, reflecting as they do the genetic mosaicism characteristic of this disease.

[Which rules apply to hypofractionated radiotherapy?]. / Radiothérapie hypofractionnée : quelles sont les règles à suivre ?

Hypofractionated radiotherapy is now more widely prescribed due to improved targeting techniques (intensity modulated radiotherapy, image-guided radiotherapy and stereotactic radiotherapy). Low dose hypofractionated radiotherapy is routinely administered mostly for palliative purposes. High or very high dose hypofractionated irradiation must be delivered according to very strict procedures since every minor deviation can lead to major changes in dose delivery to the tumor volume and organs at risk. Thus, each stage of the processing must be carefully monitored starting from the limitations and the choice of the hypofractionation technique, tumour contouring and dose constraints prescription, planning and finally dose calculation and patient positioning verification.

Bioactive lipids and the control of Bax pro-apoptotic activity.

Lipids are key regulators of cell physiology through the control of many aspects of cellular life and survival. In particular, lipids have been implicated at different levels and through many different mechanisms in the cell death program called apoptosis. Here, we discuss the action of lipids in the regulation of the activation and the integration of Bax into the mitochondrial outer membrane, a key pro-apoptotic member of the BCL-2 family. We describe how, during apoptosis, lipids can act simultaneously or in parallel as receptors or ligands for Bax to stimulate or inhibit its pro-death activity.

Underestimation of dose delivery in preclinical irradiation due to scattering conditions.

UNLABELLED: The aim of this study was to evaluate, by comparing simulation results with measurement results, the impact of the lack of scattering volume in experimental conditions of preclinical irradiation. First, a Monte Carlo model of a small animal irradiator, the Faxitron CP-160, was developed with GATE (Geant4 Application for Tomography Emission). To validate the model, simulated data were compared to depth dose and off-axis ratio profiles measured with a plane-parallel ionization chamber and Gafchromic(®) EBT films, respectively, in a solid water phantom. The AAPM TG-61 protocol was applied to measure the dose rate at the surface of a semi-infinite reference phantom. Then, the model was used to determine the dose distributions in three different phantom settings: a semi-infinite water phantom, a 2.8-cm-thick water phantom and a 2.8-cm-diameter cylindrical water phantom. The dose distributions measured and simulated with Monte Carlo methods in a semi-infinite water phantom were similar (<2%), thus validating our Monte Carlo model. The highest dose underestimation was observed between the reference and the cylindrical phantom (more than 15% difference for the entrance dose) and was due to the lack of lateral scatter and backscatter. The use of standard backscatter factors and AAPM TG-61 protocol may result in a significant underestimation of the dose absorbed by small irradiated phantoms, such as mice or cells, in preclinical studies. BACKGROUND: For preclinical radiotherapy studies, radiobiologists were used to determine the irradiation time depending only on the source surface distance. This work aimed to demonstrate that scatter conditions have a large impact on dose rate. Measurements and Monte Carlo simulations were used.