Quantitative MRI evaluation of bone marrow in sickle cell disease: relationship with haemolysis and clinical severity.

AIM: To evaluate bone marrow fat fraction using the Dixon technique (FFDix) of magnetic resonance imaging (MRI) as a potential biomarker of haemolysis and clinical severity in the overall assessment and follow-up of sickle cell disease (SCD) patients. MATERIAL AND METHODS: The present study was a cross-sectional study in which healthy individuals and SCD patients (matched for age, sex, and weight) were subjected to MRI of the lumbar spine and pelvis to quantify FFDix in the bone marrow using the Dixon technique. SCD severity was analysed by clinical and laboratory data, and an online calculator. A high degree of haemolysis was defined using the cut-off values haemoglobin (Hb) ≤10 g/dl, lactate dehydrogenase (LDH) ≥325 U/l, reticulocytes ≥3% and total bilirubin (TB) ≥1.2 mg/dl. Pearson's correlation, receiver operating characteristic (ROC) curve and binary logistic regression analysis were performed. RESULTS: Forty-eight SCD patients (26 homozygous: HbSS and 22 compound heterozygous: HbSC) and 48 healthy individuals participated in the study. FFDix was lower in SCD patients than in the control group, showing even lower values in the HbSS subtype and patients with a higher degree of haemolysis. HbSC patients with a higher degree of haemolysis using hydroxyurea (medium dosage 9.8 mg/kg/day) had lower FFDix. ROC curves and odds ratios for detecting patients with a higher degree of haemolysis at the different FFDix measurement sites demonstrated excellent performance: iliac bones (cut-off ≤16.75%, AUC = 0.824, p<0.001), femoral heads (cut-off ≤46.7%, AUC = 0.775, p=0.001), lumbar vertebrae (cut-off ≤7.8%, AUC = 0.755, p=0.002). CONCLUSION: Decreased FFDix is indicative of higher degree of haemolysis and SCD severity with great potential as a non-invasive biomarker contributing to the overall assessment and follow-up of SCD patients.

Comparative metavirome analysis in polytransfused patients.

Due to the high transfusion volume, polytransfused patients with sickle cell disease (SCD) and beta-thalassemia are constantly exposed to parenterally transmitted infections. Currently, we have little information about the virome of such patients and how the virological composition might be influenced by the hemotherapy procedures that these patients receive. The objective of this study was to compare the viral diversity between these two groups with respect to the viral abundance and how it might be affected by the specific conditions of these groups. We sequenced by next-generation sequencing (NGS) and compared the virome of 30 patients with beta-thalassemia major, 45 with SCD, and 16 blood donors from the Blood Center of Ribeirão Preto, Brazil. Predominantly, commensal viruses including Torque teno virus (TTV) genotypes and human pegiviris-1 (HPgV-1) were identified in each group. Strikingly, while HPgV-1 reads were dominant in the SCD group, thalassemic patients showed high TTV abundance, expressed both in viral reads and genotypes. We speculated that the commensal virome of polytransfused patients might be influenced by the transfusion frequency and disease characteristics and that commensal viruses might be used as important genetic biomarkers for these hematological disturbances. Nevertheless, more specific studies are necessary to confirm a relationship between blood virome and transfusion treatment.

Genotoxic and mutagenic effects of methyl ether dillapiole on the development of Aedes aegypti (Diptera: Culicidae).

Dillapiole, extracted from Piper aduncum essential oil and its derivatives, has been shown to be a potential alternative to the control of Aedes aegypti, which has become resistant to synthetic insecticides. Methyl ether dillapiole (MED) and temephos (TM) were compared to complement the data on the genotoxicity and developmental changes of Ae. aegypti. Over four generations (G1 -G4 ), third stage larvae were treated with MED at 60, 80 and 100 µg/mL and TM at 0.002, 0.005 and 0.007 µg/mL for 4 h. Adult females were separated to estimate oviposition and hatching rates, and total egg length. Over the four generations, a significant reduction was recorded in oviposition and hatching rates, and in mean egg length (Tukey, P < 0.05), compared with the negative control (NC). Cytological slide preparations were done from adult oocytes and larval neuroblasts. The cumulative effects of genotoxic (bridges, budding and nuclear fragmentation) and mutagenic (micronucleus and chromosomal breakage) damage was observed in the neuroblasts and oocytes of exposed mosquitoes. Developmental changes and damage to the genome of MED-treated Ae. aegypti were greater than those caused by TM. Further studies should focus on understanding the effects of the MED molecule on Ae. aegypti.

Comparative metavirome analysis in polytransfused patients

Due to the high transfusion volume, polytransfused patients with sickle cell disease (SCD) and beta-thalassemia are constantly exposed to parenterally transmitted infections. Currently, we have little information about the virome of such patients and how the virological composition might be influenced by the hemotherapy procedures that these patients receive. The objective of this study was to compare the viral diversity between these two groups with respect to the viral abundance and how it might be affected by the specific conditions of these groups. We sequenced by next-generation sequencing (NGS) and compared the virome of 30 patients with beta-thalassemia major, 45 with SCD, and 16 blood donors from the Blood Center of Ribeirão Preto, Brazil. Predominantly, commensal viruses including Torque teno virus (TTV) genotypes and human pegiviris-1 (HPgV-1) were identified in each group. Strikingly, while HPgV-1 reads were dominant in the SCD group, thalassemic patients showed high TTV abundance, expressed both in viral reads and genotypes. We speculated that the commensal virome of polytransfused patients might be influenced by the transfusion frequency and disease characteristics and that commensal viruses might be used as important genetic biomarkers for these hematological disturbances. Nevertheless, more specific studies are necessary to confirm a relationship between blood virome and transfusion treatment.

Comparative metavirome analysis in polytransfused patients

Due to the high transfusion volume, polytransfused patients with sickle cell disease (SCD) and beta-thalassemia are constantly exposed to parenterally transmitted infections. Currently, we have little information about the virome of such patients and how the virological composition might be influenced by the hemotherapy procedures that these patients receive. The objective of this study was to compare the viral diversity between these two groups with respect to the viral abundance and how it might be affected by the specific conditions of these groups. We sequenced by next-generation sequencing (NGS) and compared the virome of 30 patients with beta-thalassemia major, 45 with SCD, and 16 blood donors from the Blood Center of Ribeirão Preto, Brazil. Predominantly, commensal viruses including Torque teno virus (TTV) genotypes and human pegiviris-1 (HPgV-1) were identified in each group. Strikingly, while HPgV-1 reads were dominant in the SCD group, thalassemic patients showed high TTV abundance, expressed both in viral reads and genotypes. We speculated that the commensal virome of polytransfused patients might be influenced by the transfusion frequency and disease characteristics and that commensal viruses might be used as important genetic biomarkers for these hematological disturbances. Nevertheless, more specific studies are necessary to confirm a relationship between blood virome and transfusion treatment.

Peak Expiratory Flow as an Index of Frailty Syndrome in Older Adults: A Cross-Sectional Study.

OBJECTIVES: to compare the obtained and predicted peak expiratory flow (PEF) values between frail, pre-frail, and non-frail older adults; verify the association between PEF and FS; and establish cut-off points for PEF as determinants of frailty syndrome (FS). DESIGN: Cross-sectional study. LOCATION: Macapá, Amapá, Brazil. PARTICIPANTS: Community-based study community-dwelling older people. METHODS: PEF was evaluated using a peak-flow meter and FS was evaluated using Fried's frailty phenotype. The statistical analyses performed included a multinomial logistic regression model and Receiver Operating Characteristic (ROC) curves to establish cut-off points for discriminating FS. RESULTS: 409 older adults with a mean age of 70.09±7.22 years were evaluated; of these, 58.7% were pre-frail, and 12.7% were frail. PEF was lower in frail than in pre-frail participants, and lower in pre-frail than in non-frail. Frail and pre-frail older adults obtained lower PEF values than predicted. PEF (% Predicted) was inversely associated with frailty and pre-frailty even after adjustment. Cut-off points were established to discriminate the presence of frailty in older men (PEF≤350L/min; AUC=0.669; sensitivity=76.92%; specificity=52%) and women (PEF≤220L/min; AUC=0.597; sensitivity=71.79%; specificity=46.98%). CONCLUSIONS: Frail and pre-frail older adults presented significantly lower PEF than non-frail participants, and these values were lower than predicted. PEF was inversely associated with frailty and pre-frailty. PEF cut-off points can be used as a complementary method to indicate frailty in community-dwelling older adults.

Viral metagenomics in Brazilian multiply transfused patients with sickle cell disease as an indicator for blood transfusion safety.

BACKGROUND AND AIM: Patients with sickle cell disease (SCD) are submitted to multiple transfusions in order to increase the oxygen capacity of the blood, decrease blood viscosity, and suppress the sickling of the cells. Multiply transfused patients with SCD represent significant risk of acquiring parenterally transmitted infections. The analysis of the virome profile of high-risk multiply transfused patients with SCD can reveal the presence of parenterally transmitted viruses and therefore be used an indirect approach for evaluation of blood transfusion safety. MATERIALS AND METHODS: Blood samples were collected from 45 patients with SCD receiving multiple transfusions and analyzed by metagenomic analyses. The samples were assembled in pools f which were submitted to nucleic acids extraction and sequencing by Illumina NextSeq 550 equipment. For bioinformatic analysis, we used a specific in-house developed pipeline specialized in identification of emerging viruses. RESULTS: The virome composition of SCD patients revealed the presence of commensal viruses represented by anelloviruses and Human Pegivirus-1 (HPgV-1, GB virus C). Contaminant viral sequences belonging to human lentiviruses (rev, env genes), cytomegalovirus and murine leukemia virus were also identified and are attributed to vectors used in the laboratory practice. No novel or unsuspected pathogenic viruses were identified. CONCLUSION: This study evaluates for the first time the virome of multiply transfused patients with SCD. Exclusively genetic material of commensal viruses was annotated. Therefore, we believe that viral metagenomics applied in patients with high risk for acquiring parenterally transmitted infections can serve as a direct indicator for evaluation of transfusion safety.

Pediculectomy and fenestration for spinal cord decompression of the lumbar spine of a bush dog (Speothos venaticus) - case report / [Pediculectomia e fenestração para descompressão medular da coluna lombar em um cachorro-vinagre (Speothos venaticus) - relato de caso]

A captive adult male bush dog (Speothos venaticus) was referred to our Veterinary Medical Teaching Hospital from a local zoo due to a two-week history of progressive hind limb gait impairment and ataxia, non-responsive to clinical management. Computed tomography revealed decreased disc space at L3 - L4 level, with probable disc extrusion narrowing the right side of the spinal canal, compressing the spinal cord. We opted to surgically remove the disc material using both fenestration and right lateral pediculectomy (mini-hemilaminectomy) techniques. Twelve days after surgery there was mild residual proprioceptive ataxia. Gait was fully regained with remission of the neurological deficits around the 30th postoperative day. This is - to the best of our knowledge - the first successful report of a lumbar intervertebral disc extrusion in a bush dog (Speothos venaticus) surgically treated by pediculectomy and disc fenestration.(AU)

Um cachorro-vinagre (Speothos venaticus), macho, adulto, mantido em cativeiro, foi encaminhado ao Hospital Veterinário Universitário pelo zoológico local com histórico de duas semanas de comprometimento progressivo da marcha dos membros posteriores e ataxia, que não responderam ao tratamento clínico. Tomografia computadorizada revelou diminuição do espaço em disco no nível L3 - L4, com provável extrusão de disco estreitando o lado direito do canal vertebral, comprimindo a medula espinhal. Optamos por remover cirurgicamente esse material do disco usando técnicas de fenestração e pediculectomia lateral direita (mini-hemilaminectomia). Doze dias após a cirurgia, houve melhora na deambulação, com ataxia proprioceptiva residual leve. A marcha foi totalmente recuperada com remissão dos déficits neurológicos por volta do trigésimo dia de pós-operatório. Este é - até onde sabemos - o primeiro relato bem-sucedido de uma extrusão de disco intervertebral lombar em um cachorro-vinagre (Speothos venaticus) tratado cirurgicamente por pediculectomia e fenestração de disco.(AU)

Association between malocclusion and dental caries in adolescents: a systematic review and meta-analysis.

AIM: To evaluate the scientific evidence regarding the association between malocclusion and dental caries in adolescents. METHODS: Searches were conducted of six electronic databases, complemented by manual searching of the reference lists of the selected articles and grey literature. Two independent reviewers performed the selection of the articles, data extraction and the evaluation of the risks of bias through an assessment of methodological quality. Meta-analysis was performed considering the mean decayed, missing and filled teeth (DMFT) index for caries and the Dental Aesthetic Index (DAI) for malocclusion. Heterogeneity was tested using the I2 statistic and a random effect model was employed. Summary effect measures were calculated as differences in means. RESULTS: The initial search retrieved 2644 studies, only 15 of which were selected for full-text analysis. Four cross-sectional studies were included in the qualitative systematic review. Only one of these studies found no association between malocclusion and dental caries. The meta-analysis of three studies demonstrated that a lower DAI value was significantly associated with a lower mean DMFT index, except for the comparison of DAI 26-30 vs. 31-35. CONCLUSIONS: Based on the studies analysed, the scientific evidence indicates an association between malocclusion and dental caries.

Association between sense of coherence and oral health-related quality of life among toddlers.

OBJECTIVE: To assess the relationship between sense of coherence (SOC) and oral health-related quality of life (OHRQoL) among children aged one to three years. PARTICIPANTS: A cross-sectional study was conducted with 276 mother-child pairs randomly selected from the city of Diamantina, Brazil. METHOD: Information was obtained on socio-demographic factors. The short version of Antonovsky's sense of coherence scale (SOC 13) and the Early Childhood Oral Health Impact Scale (ECOHIS) were administered. The children were examined for dental caries. Statistical analysis involved descriptive statistics, the calculation of Spearman's correlation coefficients and adjusted Poisson regression models. RESULTS: SOC was significantly associated with the child's OHRQoL in the multivariate analysis. Children of mothers with high SOC (PR 0.96; 95%CI 0.93,0.98; p=0.045) had a lower prevalence of a negative impact on OHRQoL. Children with severe dental caries had a greater prevalence of a negative impact on OHRQoL (PR 2.53; 95%CI 1.77,3.62; p⟨0.001). CONCLUSIONS: Maternal SOC could be a psychosocial determinant of the OHRQoL of children aged one to three years. Severe dental caries was associated with poorer quality of life.

Maternal identification of dental caries lesions in their children aged 1-3 years.

AIM: To analyse the maternal identification of different stages of dental caries in children aged 1-3 years. METHODS: A cross-sectional study was conducted with 274 children and their mothers. The mothers answered a questionnaire on the occurrence of dental caries in their children and completed questions addressing their demographic/socio-economic status. The oral examination of the children was performed using the International Caries Detection and Assessment System. Descriptive, Chi square test and Poisson regression statistical analyses were performed. RESULTS: The prevalence of initial and established/severe dental caries lesions by age were: 1 year (23.2 and 24.2%), 2 years (17.9 and 55.7%) and 3 years (23.3 and 60.3%) respectively. Significant associations between clinical examinations and the mothers' reports were observed among children aged 1 year old who had initial stage caries lesions (p = 0.006) and in children aged 1, 2 and 3 years old who had established/severe stage caries lesions (p < 0.001). After adjustment for confounding variables it was found that mothers were more able to identify dental caries both at initial (PR 4.01, 95% CI 1.35-11.94) and established/severe stages (PR 9.14, 95% CI 2.49-33.56) in children aged 1 year old. In children aged 2 and 3 years, this identification was more evident in the established/severe stage (2 years, PR 2.98, 95% CI 1.42-6.26; 3 years, PR 2.75, 95% CI 1.09-6.93). CONCLUSIONS: Mothers of children aged 1 year old identified dental caries at initial and established/severe stages. Mothers of children aged 2 and 3 years identified dental caries only at established/severe stages.

Effect of dark discolouration and enamel/dentine fracture on the oral health-related quality of life of pre-schoolers.

AIM: To determine the effect of different types of dental trauma on oral health-related quality of life (OHRQoL) among pre-school children. METHODS: Four hundred fifty-nine Brazilian pre-schoolers aged 3-5 years were submitted to an oral examination in the school environment for the evaluation of dental trauma using the criteria proposed by Andreasen et al. (2007). Parents answered a questionnaire on the OHRQoL of the children using the Early Childhood Oral Health Impact Scale (ECOHIS) and another one on socio-demographic characteristics of the children and their families. The questionnaires were sent to the parents to be answered at home. Descriptive statistics, Mann-Whitney test and Poisson regression were used for statistical analysis. RESULTS: Children with dark discolouration and enamel-dentine fracture without pulp exposure had higher mean ECOHIS scores than those without these alterations. The multivariate regression analysis demonstrated that pre-school children with dark discolouration (PR 1.79; 95% CI 1.24-2.58) and enamel-dentine fracture without pulp exposure (PR 1.89; 95% CI 1.22-2.92) had a higher impact on quality of life than those without these alterations. CONCLUSION: Dark discolouration and enamel-dentine fracture without pulp exposure were associated with a negative impact on the life of pre-schoolers.

Leishmanicidal activity of the alkaloid-rich fraction from Guatteria latifolia.

Leishmaniasis is caused by protozoan parasites belonging to the genus Leishmania and includes cutaneous, mucocutaneous and visceral clinical forms. The drugs currently available for leishmaniasis treatment are pentavalent antimonials, amphotericin B and miltefosine, which present high toxicity, elevated cost and development of parasite resistance. The natural products constitute an important source of substances with leishmanicidal potential. Here we evaluated in vitro the anti-Leishmania amazonensis activity of crude extracts of branches, leaves and fruits of Guatteria latifolia. The branch extract (GCE) exhibited promising leishmanicidal activity against promastigotes (IC50 51.7 µg/ml), and was submitted to fractionation guided by in vitro assays. Among the seven subfractions obtained, GF1 and GF2 were the most actives against promastigotes with IC50 25.6 and 16 µg/ml, respectively. Since GCE, GF1 and GF2 were not toxic for macrophages, next, we tested their effect on intracellular amastigotes, and the IC50 values obtained were, respectively 30.5, 10.4 and 7.4 µg/ml, after 24 h treatment. The selectivity index for GCE, GF1 and GF2 were >6.5, >19.2 and > 27, respectively. Additionally, GCE, GF1 and GF2 affected the division pattern of the promastigotes by increasing 6.7, 9.4 and 7-fold the cells in Sub-G0/G1 phase, and decreasing 1.6, 2.5 and 1.8-fold the cells in G0/G1 phase, respectively. To assess the GCE and GFs capacity to modulate microbicidal mechanisms of macrophages, nitric oxide (NO) and TNF-α production were tested. Our results indicated that at the IC50s GCE, GF1 and GF2 decreased NO production of infected macrophages stimulated with IFN-γ and LPS, besides, only GF1 decreased the production of TNF-α. Our data warrant further studies of GCE, GF1 and GF2 to identify active compounds against Leishmania parasites.

The effect of monensin concentration on dry matter intake, ruminal fermentation, short-chain fatty acid absorption, total tract digestibility, and total gastrointestinal barrier function in beef heifers.

In a 4 × 4 Latin square design (24-d periods), 4 ruminally cannulated Hereford × Angus/Simmental heifers were used to evaluate the effect of increasing levels of monensin concentration on DMI, ruminal fermentation, short-chain fatty acid (SCFA) absorption across the reticulorumen, and total tract barrier function. Heifers were fed a barley-based finishing diet (76% rolled barley grain, 12% barley silage, 8% mineral and vitamin supplement, and 4% canola meal) containing 0, 22, 33 or 48 mg/kg monensin. Urinary recovery of Cr-EDTA was used as an indicator of total tract barrier function (d 18 to 20). Days 20 to 23 were used to evaluate ruminal fermentation and total tract digestibility measurements, and SCFA absorption was measured using the temporarily isolated and washed reticulorumen technique on d 24. Data were analyzed using PROC MIXED of SAS with linear and quadratic contrasts to evaluate the effect of increasing monensin dose. Increasing monensin linearly decreased DMI (10.0, 9.9, 9.3, and 9.1 kg/d for diets containing 0, 22, 33 or 48 mg/kg monensin, respectively; = 0.01) but did not affect the variation in DMI among days. Urinary Cr-EDTA recovery was not ( ≥ 0. 61) affected by increasing dose of monensin, nor was ruminal pH (mean, minimum, maximum, duration less than 5.5, and area under curve; ≥ 0.21). The acetate-to-propionate ratio linearly decreased (1.9, 1.8, 1.4, and 1.3 for diets containing 0, 22, 33 or 48 mg/kg monensin, respectively; = 0.03) with increasing monensin. There was no response ( ≥ 0. 17) for the rate of SCFA absorption with monensin concentration. Total tract ethanol soluble carbohydrate digestibility linearly increased (77.2, 84.7, 88.0, and 94.0% for diets containing 0, 22, 33 or 48 mg/kg monensin, respectively; = 0.003) whereas starch digestibility quadratically responded (93.8, 93.9, 88.0, and 94.0% for diets containing 0, 22, 33 or 48 mg/kg monensin, respectively; < 0.001), where 33 mg/kg inclusion of monensin had a minimal value. The results from this study indicate that in addition to the known effects of monensin to reduce DMI and the acetate:propionate ratio, monensin inclusion does not affect ruminal pH, SCFA absorption, or total tract barrier function.

Effect of isodillapiole on the expression of the insecticide resistance genes GSTE7 and CYP6N12 in Aedes aegypti from central Amazonia.

The yellow fever mosquito Aedes (Stegomyia) aegypti is the main vector of dengue arbovirus and other arboviruses. Dengue prevention measures for the control of A. aegypti involve mainly the use of synthetic insecticides. The constant use of insecticides has caused resistance in this mosquito. Alternative studies on plant extracts and their products have been conducted with the aim of controlling the spread of the mosquito. Dillapiole is a compound found in essential oils of the plant Piper aduncum (Piperaceae) which has been effective as a biopesticide against A. aegypti. Isodillapiole is a semisynthetic substance obtained by the isomerization of dillapiole. In the present study, isodillapiole was evaluated for its potential to induce differential expression of insecticide resistance genes (GSTE7 and CYP6N12) in 3rd instar larvae of A. aegypti. These larvae were exposed to this compound at two concentrations (20 and 40 µg/mL) for 4 h during four generations (G1, G2, G3, and G4). Quantitative RT-PCR was used to assess the expression of GSTE7 and CYP6N12 genes. GSTE7 and CYP6N12 relative expression levels were higher at 20 than at 40 µg/mL and varied among generations. The decrease in GSTE7 and CYP6N12 expression levels at the highest isodillapiole concentration suggests that larvae may have suffered from metabolic stress, revealing a potential alternative product in the control of A. aegypti.

Breast cancer under age 40: a different approach.

Breast cancer (BC) under age 40 is a complex disease to manage due to the additionally fertility-related factors to be taken in consideration. More than 90% of young patients with BC are symptomatic. Women<40 years are more likely to develop BC with worse clinicopathological features and more aggressive subtype. This has been frequently associated with inferior outcomes. Recently, the prognostic significance of age<40 has been shown to differ according to the BC subtype, being associated with worst recurrence-free survival (RFS) and overall survival (OS) for luminal BC. The biology of BC<40 has also been explored through analysis of large genomic data set, and specific pathways overexpressed in these tumors have been identified which can lead to the development of targeted therapy in the future. A multidisciplinary tumor board should determine the optimal locoregional and systemic management strategies for every individual patient with BC before the start of any therapy including surgery. This applies to both early (early breast cancer (EBC)) and advanced (advanced breast cancer (ABC)) disease, before the start of any therapy. Mastectomy even in young patients confers no overall survival advantage when compared to breast-conserving treatment (BCT), followed by radiotherapy. Regarding axillary approach, indications are identical to other age groups. Young age is one of the most important risk factors for local recurrence after both breast-conserving surgery (BCS) and mastectomy, associated with a higher risk of distant metastasis and death. Radiation after BCS reduces local recurrence from 19.5 to 10.2% in BC patients 40 years and younger. The indications for and the choice of systemic treatment for invasive BC (both early and advanced disease) should not be based on age alone but driven by the biological characteristics of the individual tumor (including hormone receptor status, human epidermal growth factor receptor 2 (HER-2) status, grade, and proliferative activity), disease stage, and patient's comorbidities. Recommendations regarding the use of genomic profiles such as MammaPrint, Oncotype Dx, and Genomic grade index in young women are similar to the general BC population. Especially in the metastatic setting, patient preferences should always be taken into account, as the disease is incurable. The best strategy for these patients is the inclusion into well-designed, independent, prospective randomized clinical trials. Metastatic disease should always be biopsied whenever feasible for histological confirmation and reassessment of biology. Endocrine therapy is the preferred option for hormone receptor-positive disease (HR+ve), even in presence of visceral metastases, unless there is concern or proof of endocrine resistance or there is a need for rapid disease response and/or symptom control. Recommendations for chemotherapy (CT) should not differ from those for older patients with the same characteristics of the metastatic disease and its extent. Young age by itself should not be an indication to prescribe more intensive and combination CT regimens over the sequential use of monotherapy. Poly(ADP-ribose) polymerase inhibitors (PARP inhibitors) represent an important group of promising drugs in managing patients with breast cancer susceptibility gene (BRCA)-1- or BRCA-2-associated BC. Specific age-related side effects of systemic treatment (e.g., menopausal symptoms, change in body image, bone morbidity, cognitive function impairment, fertility damage, sexual dysfunction) and the social impact of diagnosis and treatment (job discrimination, taking care for children) should also be carefully addressed when planning systemic long-lasting therapy, such as endocrine therapy. Survivorship concerns for young women are different compared to older women, including issues of fertility, preservation, and pregnancy.

Vertical forces assessment according to radiographic hip grade in German shepherd dogs.

OBJECTIVE: To investigate the correlation between radiographic hip grade and kinetic parameters in German shepherd dogs. METHODS: Dogs were distributed into five groups of eight dogs each according to hip grade (A, B, C, D or E). Dogs were submitted to clinical evaluation and kinetic analysis. Five valid passages were analysed using data collected from a pressure walkway. Peak vertical force, vertical impulse and stance phase duration were evaluated at velocity (1 · 2 to 1 · 4 m/s) ±0 · 1 m/s(2) acceleration. Kinetic data between groups were compared. RESULTS: In pelvic limbs, mean peak vertical force decreased progressively from grade C (mild) to grade E (severe) hip dysplasia. The vertical impulse was decreased in groups C and E compared to groups A, B and D; stance phase duration did not differ significantly between groups. CLINICAL SIGNIFICANCE: Mean peak vertical force was lower in dogs with severe hip dysplasia compared with mildly dysplastic dogs. These results suggest that hip dysplasia degree can affect lameness severity.

Meniscal transection rather than excision increases pain behavior and structural damage in experimental osteoarthritis in mice.

OBJECTIVE: To evaluate pain behavior and structural damage in mice subjected to either meniscal transection or removal. METHODS: Mice (10/group) were subjected to transection of the medial collateral and anterior cruciate ligaments (ACLT/MCLT) followed by either transection (meniscotomy) or removal (meniscectomy) of the medial meniscus. A control group was subjected only to transection of the ligaments. Pain was assessed using the electronic pressure-meter paw test. Cell influx, measured in joint exudates, and joint histopathology were assessed after 49 days. Four other groups subjected to meniscotomy received indomethacin, the inducible nitric oxide synthase (iNOS) inhibitor 1400W, morphine or the vehicles. RESULTS: Both meniscotomy and meniscectomy groups displayed persistent and significant increase in pain behavior as compared to controls, being significantly more severe in the former. Cell influx was more intense in the meniscotomy as compared to the meniscectomy group. Structural damage at the tibia, but not at the femur, was also more severe in the meniscotomy group. Indomethacin and 1400W partially but significantly reduced pain whereas morphine abrogated pain behavior in meniscotomized mice. CONCLUSION: Meniscal transection rather than resection promotes more severe pain and structural damage in mice. Administration of opioids, cyclooxygenase and nitric oxide (NO) synthase inhibitors provide analgesia in this model. Careful description of the structures damaged is crucial when reporting experimental osteoarthritis (OA).