Secreted factors derived from obese visceral adipose tissue regulate the expression of breast malignant transformation genes.

BACKGROUND/OBJECTIVES: Obese adipose tissue, especially the visceral depot, exhibits altered production of several molecules that could have a role on the initiation/promotion of breast cancer development. The aim of this work was to evaluate the effect of excess adipose tissue and its secreted factors on the expression of genes involved in the early steps of tumor promotion on the mammary gland. SUBJECTS AND METHODS: Carcinogenesis-related gene expression was evaluated in mammary gland tissue from female diet-induced obese (DIO) Sprague-Dawley rats and circulating leukocytes isolated from a group of breast cancer diagnosed and non-diagnosed obese women and compared with their normal weight counterparts. In addition, the human non-tumoral mammary epithelial cell line MCF10A was treated in vitro with the visceral (retroperitoneal adipose tissue (RPAT)) or subcutaneous adipose tissue (SAT) secretome and with rising concentrations of the lipid peroxidation by-product 4-hydroxynonenal (4-HNE). RESULTS: DIO rats were classified as susceptible to DIO (DIO-S) or partially resistant to DIO (DIO-R) according to the maximum fat mass gain of the lean group as a cut-off. As compared with lean and DIO-R, the DIO-S group showed a higher fat mass and lower lean mass. The anatomical characteristic of DIO-S was correlated with differential expression of cellular proliferation (ALDH3A1 and MYC) and antioxidant and DNA protection (GSTM2, SIRT1), and tumor suppression (TP53, PTEN, TGFB1) genes. Remarkably, this carcinogenesis-related gene expression pattern was reproduced in MCF10A treated with the RPAT secretome from DIO-S rats and with the lipid peroxidation by-product 4-HNE. Moreover, this pattern was also detected in leukocytes from obese women compared with normal weight women without evidence of breast cancer. CONCLUSIONS: Lipid peroxides secreted by the obese visceral adipose tissue could be among the relevant factors that promote changes involved in the early steps of tumor development in mammary gland. These changes can be detected even before histological alterations and in circulating leukocytes.

Meat quality attributes of male and female broilers from 4 commercial strains processed for 2 market programs.

In recent times, meat quality has become a key aspect of poultry production. In the current study, 2,400 sex separate broilers from 4 commercial strains were placed in 6 replications to evaluate various meat quality characteristics when grown to 2 market weights. Broilers were fed 1 of 2 diets with varying degrees of amino acid inclusion to evaluate meat quality of broiler raised on varying planes of nutrition. Birds were processed to meet 2 specified target weights (2.5 and 3.8 kg) representing small bird and big bird debone markets in the United States, respectively. Birds were processed using commercial methods, deboned at 3-h postmortem, and meat quality was assessed. Myopathies (woody breast, white striping, spaghetti meat, along with tenderloin quality), fillet dimensions, color, water-holding capacity (e.g., drip loss, cook loss), and Meullenet Owens Razor Shear was determined. Data were analyzed using the Mixed Model platform of JMP Pro 15.2 (SAS Institute, Cary, NC). Diet had no effect (P > 0.05) on the key quality responses; data were then pooled resulting in main effects of sex, strain, and target weight (noted as carcass size). On the day of processing, high yielding (HY) strains produced higher breast and tender yields (P < 0.05) when compared to standard yielding (SY) strains. In addition, and as expected, females exhibited higher breast and tender yields (P < 0.05) than males. However, males had significantly thicker (P < 0.05) and longer (P < 0.05) fillets, higher incidences (P < 0.05) of white striping, and higher (P < 0.05) cook loss when compared to females. Differences were also observed in tenderness as SY strain A produced the lowest shear values, whereas SY strain B produced the highest shear values across parameters (P < 0.05). SY strains in the small bird (SB) market performed better than SY strains in the big bird (BB) market as indicated by lower incidences of breast and tender myopathies white striping, woody breast, spaghetti meat, woody-like tender, and tender feathering and improved quality attributes (P < 0.05). Similar trends were observed (P < 0.05) in HY strains as SB carcasses produced a better overall product than BB. Differences in carcass size directly impacted quality (P < 0.05) as SB markets showed improvements in most parameters assessed, but broilers representing BB markets had greater breast yield. Although strain had minimal impacts on quality measures, carcass size, and sex had a greater impact on muscle myopathies, water-holding capacity, and shear properties.

Assessment of meat quality attributes of four commercial broiler strains processed at various market weights.

As the demand for poultry meat continues to rise, industry production is constantly challenged with obtaining consumer needs. Integrators have answered this increasing demand by improving the growth rate of broilers allowing for increased production efficiently. The resulting broiler produces higher yields and a larger quantity of fresh poultry to satisfy consumer needs. However, this increase in efficiency has cost integrators as new quality issues continue to manifest through global production. Therefore, the objective of the current experiment was to evaluate the effect of genetic strain (standard and high yielding) and target weight on meat quality attributes such as pH, water holding capacity (WHC), and tenderness, alongside meat quality defects such as breast and tender myopathies. In the current study, 1,800 broilers from 4 commercial strains (2 high breast yielding (HY) and 2 standard yielding (SY) were raised sex separate to evaluate meat quality trends over time at 6 previously defined market weights. Birds were processed at weights ranging from 2,043 to 4,313 g in 454 g increments. HY strains produced higher breast and tender yields than those of SY strains (P < 0.05). There was an increase in breast and tender yield as target weight increased (P < 0.05) for both HY and SY strains. Differences were observed between strains for all fillet dimensions (P < 0.05); however, these measurements increased as target weight increased as expected. Woody breast (WB) had a higher severity (P < 0.05) in HY strains over SY strains, for both males and females. Differences were observed in white striping (WS; P < 0.05) for females in both strains, but no differences were observed in males. A main effect of target was noticed for both WB and WS (P < 0.05), expressing increased severity as target weight increased. Shear values were influenced more by target weight (P < 0.05), but inconsistent differences were observed between HY and SY groups. Meullenet-Owens Razor Shear (MORS) energy values increased slightly as target weights increased (P < 0.05) from 2,951 to 4,313 g in both males and females, but differences were minor and inconsistent with the smaller carcass weights. The MORS peak counts generally increased as target weight increased for both sexes. While strain had minimal effects on meat quality attributes, processing weight had a greater influence on quality, specifically muscle myopathies, WHC, and shear properties.

Association of breast cancer and obesity in a homogeneous population from Spain.

OBJECTIVE: To evaluate for the first time in Spain if the association between obesity and breast cancer prognosis is similar to that reported in other countries with non Mediterranean dietary patterns. METHODS: Weight and height and other variables of interest, tumor characteristics and current clinical status 3 yr after diagnosis were retrieved from medical files of breast cancer women diagnosed during 2006. A total of 159 cases with complete information were studied and categorized according to the World Health Organization criteria in normal-/under-weight, overweight, and obese. RESULTS: Among breast cancer patients, 70.4% were classified as overweight/ obese and 29.6% as normal weight. Prevalence of obesity was high (38.4%) in comparison with information reported for healthy women of the same region (27.11%) and was higher among post-menopausal patients and in women with low level of alcohol and tobacco consumption. Moreover, overweight/ obese cases (79.5%) tended to have more often human epidermal growth factor receptor 2 status negative when compared with those with normal weight (70.2%; p=0.097) and the survival curves tended to be influenced by body mass index although without statistical significance. CONCLUSIONS: Overweight/obesity in a Mediterranean country is highly prevalent among breast cancer patients. Our results support a putative influence of obesity per se and not the alimentary patterns as a prognostic factor in breast cancer patients justifying the need to perform larger prospective studies.

A comparison of formic acid or monoglycerides to formaldehyde on production efficiency, nutrient absorption, and meat yield and quality of Cobb 700 broilers.

After being banned by the European Commission in 2018, the use of formaldehyde as a feed amendment in the United States has come into question. Therefore, this study was conducted to explore alternatives to formaldehyde, such as formic acid and monoglycerides, and their effects on poultry production. In total, 1,728 Cobb 700 broilers were randomly assigned to 96-floor pens on day of hatch (18 birds/pen). Using a randomized complete block design (4 blocks), treatments were assigned to pens with blocking based on location within the barn, with the eastern half of the barn designated for digestibility and the western half designated for production (per experiment: 8 control pens and 10 pens per treatment). All diets were based on a negative control (NC), basal diet. Dietary treatments consisted of: NC, NC + 0.25% formalin (F), NC + 0.25 and 0.50% Amasil NA (AML and AMH; 61% formic acid and 20.5% Na-formate), and NC + SILO Health 104L (SILO; mixture of monoglycerides; 0.5% from 0 to 14 d, 0.4% from 14 to 28 d, and 0.2% from 28 to 42 d). Water and feed were provided ad libitum. Performance data were collected during feed changes on d 0, 14, 28, and 42, with digestibility data collected at d 14 (2 per pen) and carcass quality (6 per pen) assessed at d 46 with a randomly selected group of broilers. A one-way ANOVA followed by Dunnett's multiple comparison, where treatments were evaluated against F were conducted using JMP 14.0 (P ≤ 0.05). Main effect of treatment was significant for performance, nutrient digestibility, and carcass quality. Differences in body weight and ADG were observed from d 14 to d 28, resulting in a trending improvement in lysine digestibility on d 14 and carcass quality on d 46 of birds fed AML and AMH in comparison to those fed F (P < 0.05). Whereas birds fed SILO had reduced digestibility of methionine on d 14 and a decrease in meat quality on d 46 in comparison to those fed F (P < 0.05). Therefore, Amasil NA at 0.25 or 0.50% may be an effective alternative to formaldehyde as a feed amendment for poultry production.

SEOM clinical guidelines for cervical cancer (2019).

Cervical cancer (CC) is the fourth most common cancer in women worldwide, strongly linked to high-risk human papilloma virus infection. In high-income countries, the screening programs have dramatically decreased the incidence of CC; however, the lack of accessibility to them in developing countries makes CC an important cause of mortality. Clinical stage is the most relevant prognostic factor in CC. The new FIGO staging system published in 2018 is more accurate than the previous one since it takes into account the lymph node status. In early stages, the primary treatment is surgery-with some concerns recently raised regarding minimally invasive surgery because it might decrease survival-or radiotherapy, whereas concomitant chemo-radiotherapy is the conventional approach in locally advanced stages. For recurrent or metastatic CC, the combination of chemotherapy plus bevacizumab is the preferred therapy. Immunotherapy approach based on checkpoint inhibitors is evolving as the election therapy following failure to platinum therapy.

Paclitaxel and cisplatin in the treatment of metastatic non-small-cell lung cancer during pregnancy.

The concomitant occurrence of cancer during pregnancy is a rare event. The cancers most frequently detected during pregnancy are breast, cervical, melanoma, ovarian, leukaemia and lymphoma, however the diagnosis of lung cancer during pregnancy is particularly exceptional. In this case, we report on a pregnant woman who was diagnosed with non-small-cell lung cancer and received therapy with paclitaxel and cisplatin.

Galician consensus on management of cardiotoxicity in breast cancer: risk factors, prevention, and early intervention.

This Galician consensus statement is a joint oncologists/cardiologists initiative indented to establish basic recommendations on how to prevent and to manage the cardiotoxicity in breast cancer with the aim of ensuring an optimal cardiovascular care of these patients. A clinical screening of the patients before treatment is recommended to stratify them into a determined risk group based on their intrinsic cardiovascular risk factors and those extrinsic arose from breast cancer therapy, thereby providing individualized preventive and monitoring measures. Suitable initial and ongoing assessments for patients with low and moderate/high risk and planned treatment with anthracyclines and trastuzumab are given; also, measures aimed at preventing and correcting any modifiable risk factor are pointed out .

Gemcitabine plus vinorelbine for the treatment of advanced non-small cell lung cancer.

The aim of this study was to determine the clinical activity and toxicity of a novel chemotherapy regimen of weekly gemcitabine and vinorelbine in patients with advanced non-small cell lung cancer (NSCLC). 40 chemotherapy-naïve patients with stage IIIB/IV NSCLC were included. The doses of gemcitabine and vinorelbine were 1000 and 25 mg/m(2), respectively, given on days 1, 8 and 15, every 28 days. 38 patients were evaluable for response. One patient achieved a complete response (CR) and 10 attained a partial response (PR), for an overall response rate (ORR) of 29% (95% confidence interval (CI): 15-43%). 47% of patients experienced a clinical benefit. The main toxicity consisted of grade 3 anaemia and neutropenia in 5% of patients. Non-haematological toxicity was minimal. The dose-intensities were 744 mg/m(2)/week for gemcitabine and 15 mg/m(2)/week for vinorelbine. 40% of the patients survived for longer than 1 year. The median time to progression was 4 months and the median survival 8.5 months (95% CI: 3.1-13.8 months). The weekly administration of gemcitabine and vinorelbine is very well tolerated and results in an acceptable response rate for the treatment of NSCLC.

Psychopharmacology in child and adolescent psychiatry: a review of the past seven years. Part I.

OBJECTIVE: To present a critical overview of the literature published in the past 7 years on the efficacy and safety of psychoactive agents in mental retardation with associated psychiatric disorders, autistic disorder, Tourett's disorder, and attention-deficit/hyperactivity disorder. METHOD: Double-blind and placebo-controlled clinical trials and open studies were reviewed and selected reports presented. RESULTS: The literature review reveals that progress has been made in the psychopharmacological treatment of the above conditions. This is partly because more studies use larger sample sizes and a narrower age range of diagnostically homogeneous patients and use a more sophisticated methodology than in previous years. Greater attention is being paid to a critical assessment of psychoactive agents and to their safety, to the efficacy as well as to the effectiveness of drugs. The 5-year National Plan for Research on Child and Adolescent Mental Disorders (1991) based on the Institute of Medicine Report (1989) already has had a significant impact on psychophamacology research. CONCLUSIONS: Advances in methodology, initiatives of the National Institute of Mental Health, and the advent of DSM-IV should continue to enhance research and improve pharmacotherapy in clinical practice.

Psychopharmacology in child and adolescent psychiatry: a review of the past seven years. Part II.

OBJECTIVE: To present a critical overview of the selected literature published in the past 7 years on the efficacy and safety of psychoactive agents in conduct disorder, schizophrenia, separation anxiety disorder, selective mutism, obsessive-compulsive disorder, panic disorder, major depressive disorder, bipolar disorder, and sleep and eating disorders. METHOD: Reports of double-blind and placebo-controlled trials and open studies were reviewed and selected studies presented. RESULTS: Employment of larger samples of diagnostically homogeneous patients and a more sophisticated design and methodology led to progress in the treatment of most of these conditions. Data have been accumulated on dose range and safety of lithium in this age group, and there is supportive evidence that lithium is useful in reducing aggression. CONCLUSIONS: For a rational treatment approach, further studies are needed, particularly in depression and conduct disorder; psychosocial-environment contributions and possible biological markers should be investigated in order to identify children who require psychopharmacological treatments and those who will respond to psychosocial interventions or the combination of both. Symptoms targeted to require pharmacotherapy and symptoms targeted to respond to psychosocial interventions have to be identified.

Treatment of autistic disorder.

OBJECTIVE: To present an overview of a variety of treatment approaches in individuals with autistic disorder. METHOD: Selected studies and articles are reviewed. RESULTS: In the past three decades, great progress has been made in the treatment of autistic disorder, particularly in the area of education and parental involvement, with the objective to transfer to home and in other situations learning acquired in school. A role for psychoactive agents, when combined with psychosocial treatments, has been identified. CONCLUSIONS: Although considerable advances have been made in a variety of interventions-educational, psychosocial, and biological-knowledge about the comparative and combined efficacy of the various treatment modalities is lacking. From the parents' perspective, particularly, support and continuity of services require improvement.

Carbamazepine in aggressive children with conduct disorder: a double-blind and placebo-controlled study.

OBJECTIVE: To assess critically the short-term efficacy and safety of carbamazepine in the reduction of aggressiveness in children with diagnosed conduct disorder. METHOD: Subjects were children aged 5 to 12 years who were hospitalized for treatment-resistant aggressiveness and explosiveness and who had diagnosed conduct disorder. The study was double-blind and placebo-controlled, using a parallel-groups design. Following a 2-week placebo baseline period, children who met the aggression criteria were randomly assigned to treatments for 6 weeks; the study ended with a 1-week posttreatment placebo period. Multiple raters rated the children independently, using multiple rating scales under four conditions. The main outcome measures included the Overt Aggression Scale, the Global Clinical Judgments (Consensus) Scale, and the Children's Psychiatric Rating Scale. RESULTS: Twenty-two children, aged 5.33 to 11.7 years, completed the study. Carbamazepine was not superior to placebo at optimal daily doses ranging from 400 to 800 mg, mean 683 mg, at serum levels of 4.98 to 9.1 micrograms/mL. Untoward effects associated with administration of carbamazepine were common. CONCLUSIONS: In this modest sample of children, the superiority of carbamazepine over placebo in reducing aggressive behavior was not demonstrated.

A pilot study of clomipramine in young autistic children.

OBJECTIVE: To assess the short-term efficacy and safety of clomipramine in hospitalized young children with autism. METHOD: This was an open pilot study; after a 1-week placebo baseline, subjects were treated with clomipramine for 5 weeks. Dosage was individually regulated; starting dose was 25 mg/day; increments were 25 mg/day. Maximum dose was 250 mg/day or 5.0 mg/kg per day, whichever was less. Multiple raters, under several conditions, used the Children's Psychiatric Rating Scale, Clinical Global Impressions, Conners Parent Teacher Questionnaire, and the Clinical Global Consensus Ratings. RESULTS: Eight children, aged 3.5 to 8.7 years, were enrolled in the study; seven of these completed the study. A 3.5-year-old boy was excluded during the third week of treatment after having urinary retention on two occasions. At doses ranging from 2.50 to 4.64 mg/kg per day (mean = 3.14), one child improved moderately and six were rated as worse on the Clinical Global Consensus Ratings. Untoward effects were common. CONCLUSIONS; Clomipramine was not therapeutic and was associated with serious untoward effects in this sample. Young autistic children may be more prone to experience untoward effects than older patients.

Spectrophotometric and chromatographic detection of Karwinskia humboldtiana (tullidora) toxin in rat serum after tullidora ingestion.

The absorbance spectrum of tullidinol, a tullidora (Karwinskia humboldtiana) toxin, showed peaks at 260 and 410 nm when dissolved in ethanol; the second peak was linearly related to toxin concentration. Silica gel thin layer chromatograms of tullidinol solutions showed a single, yellow spot with an Rf of 0.76. A single dose of tullidora fruit homogenate was orally given to male Wistar rats; the absorbance spectrum of serum from tullidora-treated rats showed peaks at 300 nm and at 410 nm; the second peak was absent in serum from control rats. No spots were detected in chromatograms of normal serum, but a yellow spot with the same Rf as that of tullidinol was found in the serum of tullidora-treated rats. We conclude that tullidinol was detected in the serum of treated animals and that the methods we used for its detection may also help to diagnose accidental tullidora poisoning in cattle and human beings.

The role of SPECT brain imaging in assessing psychopathology in the medically ill.

Cerebral single photon emission computed tomography (SPECT), a method of functional brain imaging, measures cerebral blood flow and metabolism. This paper describes the imaging procedure and several cases where cerebral SPECT was of use in the differential diagnosis of medically ill patients who also presented with psychopathology. SPECT patterns in cerebrovascular disease, dementia, focal epilepsy, and AIDS are at present the best described and seem to be the most specific. Often changes in regional cerebral blood flow are seen before structural changes become apparent on CT or MRI. Cerebral SPECT can add valuable diagnostic information in assessing psychopathology in the medically ill and can often lead to changes in treatment.

Single-photon emission computed tomography of the brain in acute mania and schizophrenia.

Single-photon emission computed tomography (SPECT) imaging with n-isopropyliodoamphetamine (IMP) was performed on 11 patients with bipolar mania, 21 acute schizophrenics, and 15 healthy control subjects. Subjects were evaluated with neuropsychological tests and psychiatric rating scales. SPECT brain studies were blindly evaluated to assess the degree of radiopharmaceutical uptake in three neuroanatomical regions of interest in each hemisphere. All the control subjects, 1 manic patient, and 1 schizophrenic patient had normal brain SPECT uptake patterns. The scans of all others were read as abnormal. Hypofrontality was noted in some schizophrenics and maniacs. A significant increase in tracer uptake in temporal lobes was observed in both patient groups, more prominently in the manic patients. Increased and decreased basal ganglia uptake was also observed in patients. Both manic and schizophrenic patients showed cortical tracer heterogeneity of varying degree. The patterns of cerebral SPECT uptake seen in these acute psychoses were not specific for a diagnosis, but may be associated with dimensions of psychopathology. Because the patterns are different from those seen in cerebrovascular disease and the dementias, they may prove to be helpful in differential diagnosis.

Anterior fontanel herniation in group B streptococcus meningitis in newborns.

Brain herniation at any site is a rare complication of neonatal meningitis. Two cases of anterior fontanel herniation, associated with group B beta-hemolytic streptococcus meningitis are reported. This finding is a poor prognostic sign.

Posttraumatic childhood lumbosacral plexus neuropathy.

A 13-month-old male received crush injury to the abdomen resulting in paraparesis due to lumbosacral plexus neuropathy. The child was monitored with serial clinical examinations and electromyography/nerve conduction studies. He had complete clinical recovery. Lumbosacral plexus neuropathy is unusual in childhood and has not been previously reported as a result of abdominal trauma. This patient is presented with details of the clinical course, electrodiagnostic studies, discussion, and literature review.

[Polyuric dilatation of the urinary tract in congenital nephrogenic diabetes insipidus. Clinical and diagnostic aspects. Presentation of a case and review of the literature]. / La dilatación poliúrica del tracto urinario en diabetes insípida nefrogénica congénita. Aspectos clínicos y diagnósticos. Presentación de un caso con atrofia renal. Revisión de la literatura.

Massive polyuria existing in congenital nephrogenic diabetes insipidus can cause a more or less severe dilatation of the urinary tract in absence of obstruction. Clinical and diagnostic aspects of this pathology are presented relating then with other types of diabetes insipidus. One case of bilateral severe dilatation with evolution towards renal atrophia is presented. Mechanical obstruction was discarded. The disease was refractory to urinary concentration tests and therapy to reduce urine volume. The possible etiopathological mechanisms of functional obstruction and surgical alternatives directed to preserve the kidney function are explained and discussed. The current literature is reviewed but the cases reported are few due to the low incidence of urological affectation. Presence of kidney atrophia is exceptional.