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1.
Actas Dermosifiliogr ; 115(3): 293-297, 2024 Mar.
Article in English, Spanish | MEDLINE | ID: mdl-37871891

ABSTRACT

Although subungual melanoma is uncommon, it is associated with worse outcomes than melanomas in other locations and accounts for 1% to 23% of all melanomas, depending on the population. The aim of this study was to describe the clinical and histopathologic features of subungual melanoma in a Mexican population. We identified 303 patients with melanoma, and of these, 19% (57 patients with a median age of 71 years) had subungual melanoma. The main sites affected were the lower limbs (52.6%) and the toe (75.4%). The most common histologic subtype was acral lentiginous melanoma (50.9%). Median Breslow thickness was 3 mm, and stage IA tumors were the most common (in 28.1% of patients). Recurrence and metastasis occurred in 19.3% and 8.8% of patients, respectively. The clinical and histopathologic features identified are similar to those described in the literature. Early diagnosis and treatment are crucial for improving prognosis.


Subject(s)
Melanoma , Nail Diseases , Skin Neoplasms , Humans , Aged , Melanoma/pathology , Cohort Studies , Skin Neoplasms/pathology , Nail Diseases/diagnosis , Prognosis
2.
Actas Dermosifiliogr ; 115(3): T293-T297, 2024 Mar.
Article in English, Spanish | MEDLINE | ID: mdl-38242433

ABSTRACT

Although subungual melanoma is uncommon, it is associated with worse outcomes than melanomas in other locations and accounts for 1% to 23% of all melanomas, depending on the population. The aim of this study was to describe the clinical and histopathologic features of subungual melanoma in a Mexican population. We identified 303 patients with melanoma, and of these, 19% (57 patients with a median age of 71 years) had subungual melanoma. The main sites affected were the lower limbs (52.6%) and the toe (75.4%). The most common histologic subtype was acral lentiginous melanoma (50.9%). Median Breslow thickness was 3 mm, and stage IA tumors were the most common (in 28.1% of patients). Recurrence and metastasis occurred in 19.3% and 8.8% of patients, respectively. The clinical and histopathologic features identified are similar to those described in the literature. Early diagnosis and treatment are crucial for improving prognosis.


Subject(s)
Melanoma , Nail Diseases , Skin Neoplasms , Humans , Aged , Melanoma/pathology , Cohort Studies , Skin Neoplasms/pathology , Nail Diseases/diagnosis , Prognosis
3.
Med Oral Patol Oral Cir Bucal ; 28(3): e217-e228, 2023 May 01.
Article in English | MEDLINE | ID: mdl-37026607

ABSTRACT

BACKGROUND:  Oral decay prior to a hospital medical-surgical procedure is a risk factor for the development of postoperative complications. However, perioperative oral practices as a protective factor have not been studied. This review aims to evaluate the effectiveness of perioperative oral practices in the reduction of risk of developing postoperative complications in in-hospital medical surgical procedures. MATERIAL AND METHODS: This review and meta-analysis was conducted according to Cochrane guidelines. Medline, Scopus, Scielo, and Cochrane were consulted. Articles of the previous 10 years concerning adult patients undergoing perioperative oral practices prior to hospital medical-surgical procedures, were included. Data of the type of perioperative oral practice, type of postoperative complication and measures of effect on the development of complications were extracted. RESULTS: Of a pool of 1470 articles, 13 were included for systematic review and 10 for meta-analysis. The most common perioperative oral procedures were focalized approach (FA), referred to only the elimination of infectious foci in the oral cavity and comprehensive approach (CA), referred to a integral approach of the patient's oral health, both of which were mainly performed in oncologic surgeries, both were effective in the reduction of postoperative complications (RR=0.48, [95% CI 0.36 - 0.63]). The most reported postoperative complication was postoperative pneumonia. CONCLUSIONS: Perioperative oral management proved to be a protective factor against the development of postoperative complications.


Subject(s)
Hospitals , Postoperative Complications , Adult , Humans , Incidence , Length of Stay , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/prevention & control
4.
Br J Dermatol ; 182(1): 147-155, 2020 01.
Article in English | MEDLINE | ID: mdl-31049933

ABSTRACT

BACKGROUND: The malignant mechanisms that control the development of cutaneous T-cell lymphoma (CTCL) are beginning to be identified. Recent evidence suggests that disturbances in specific intracellular signalling pathways, such as RAS-mitogen-activated protein kinase, T-cell receptor (TCR)-phospholipase C gamma 1 (PLCG1)-nuclear factor of activated T cells (NFAT) and Janus kinase (JAK)-signal transducer and activator of transcription (STAT), may play an essential role in the pathogenesis of CTCL. OBJECTIVES: To investigate the mechanisms controlling disease development and progression in mycosis fungoides (MF), the most common form of CTCL. METHODS: We collected 100 samples that were submitted for diagnosis of, or a second opinion regarding, MF between 2001 and 2018, 80% of which were in the early clinical stages of the disease. Formalin-fixed paraffin-embedded tissues were used for histological review and to measure the expression by immunohistochemistry of surrogate markers of activation of the TCR-PLCG1-NFAT, JAK-STAT and NF-κB pathways. Folliculotropism and large-cell transformation were also examined. RESULTS: NFAT and nuclear factor kappa B (NF-κB) markers showed a comparable activation status in early and advanced stages, while STAT3 activation was more frequent in advanced stages and was associated with large-cell transformation. Consistently with this observation, STAT3 activation occurred in parallel with MF progression in two initially MF-negative cases. A significant association of NFAT with NF-κB markers was also found, reflecting a common mechanism of activation in the two pathways. Genomic studies identified nine mutations in seven genes known to play a potential role in tumorigenesis in T-cell leukaemia/lymphoma, including PLCG1, JAK3 and STAT3, which underlies the activation of these key cell-survival pathways. A higher mutational allele frequency was detected in advanced stages. CONCLUSIONS: Our results show that STAT3 is activated in advanced cases and is associated with large-cell transformation, while the activation of NFAT and NF-κB is maintained throughout the disease. These findings could have important diagnostic and therapeutic implications. What's already known about this topic? Mycosis fungoides is characterized by a clonal expansion of T cells in the skin. The mechanisms controlling disease development and progression are not fully understood. What does this study add? An association of the nuclear factor of activated T cells and nuclear factor kappa B pathways was found, which could reflect a common mechanism of activation. These pathways were activated in early and advanced stages at the same level. Signal transducer and activator of transcription 3 activation was associated with large-cell transformation and was more frequent in advanced stages. A genomic analysis of cutaneous T-cell lymphoma-associated genes was performed. Nine mutations were detected. What is the translational message? These results could have important implications for the treatment of MF in the near future.


Subject(s)
Lymphoma, T-Cell, Cutaneous , Mycosis Fungoides , NF-kappa B , NFATC Transcription Factors , STAT3 Transcription Factor , Skin Neoplasms , Humans , Mycosis Fungoides/genetics , STAT3 Transcription Factor/genetics , STAT3 Transcription Factor/metabolism , Skin Neoplasms/genetics , T-Lymphocytes/metabolism
5.
Neural Plast ; 2020: 8869669, 2020.
Article in English | MEDLINE | ID: mdl-33029122

ABSTRACT

Microtus ochrogaster is a rodent with a monogamous reproductive strategy characterized by strong pair bond formation after 6 h of mating. Here, we determine whether mating-induced pair bonding increases cell proliferation in the subventricular zone (SVZ), rostral migratory stream (RMS), and dentate gyrus (DG) of the hippocampus in male voles. Males were assigned to one of the four groups: (1) control: males were placed alone in a clean cage; (2) social exposure to a female (SE m/f): males that could see, hear, and smell a sexually receptive female but where physical contact was not possible, because the animals were separated by an acrylic screen with small holes; (3) social exposure to a male (SE m/m): same as group 2 but males were exposed to another male without physical contact; and (4) social cohabitation with mating (SCM): males that mated freely with a receptive female for 6 h. This procedure leads to pair bond formation. Groups 2 and 3 were controls for social interaction. Male prairie voles were injected with 5-bromo-2'-deoxyuridine (BrdU) during the behavioral tests and were sacrificed 48 h later. Brains were processed to identify the new cells (BrdU-positive) and neuron precursor cells (neuroblasts). Our principal findings are that in the dorsal region of the SVZ, SCM and SE m/f and m/m increase the percentage of neuron precursor cells. In the anterior region of the RMS, SE m/f decreases the percentage of neuron precursor cells, and in the medial region SE m/f and m/m decrease the number of new cells and neuron precursor cells. In the infrapyramidal blade of the subgranular zone of the DG, SE m/m and SCM increase the number of new neuron precursor cells and SE m/m increases the percentage of these neurons. Our data suggests that social interaction, as well as sexual stimulation, leads to pair bonding in male voles modulating cell proliferation and differentiation to neuronal precursor cells at the SVZ, RMS, and DG.


Subject(s)
Cell Proliferation , Hippocampus/physiology , Lateral Ventricles/physiology , Neurogenesis , Pair Bond , Social Behavior , Animals , Arvicolinae , Female , Male , Neural Stem Cells/physiology , Neurons/physiology
6.
Horm Behav ; 97: 47-55, 2018 01.
Article in English | MEDLINE | ID: mdl-29111331

ABSTRACT

In rodents, sexual stimulation induces a positive affective state that is evaluated by the conditioned place preference (CPP) test. Opioids are released during sexual behavior and modulate the rewarding properties of this behavior. Prairie voles (Microtus ochrogaster) are a socially monogamous species, in which copulation with cohabitation for 6h induces a pair bond. However, the mating-induced reward state that could contribute to the establishment of the long-term pair bond has not been evaluated in this species. The present study aimed to determine whether one ejaculation or cohabitation with mating for 6h is rewarding for voles. We also evaluated whether this state is opioid dependent. Our results demonstrate that mating with one ejaculation and social cohabitation with mating for 6h induce a CPP in males, while exposure to a sexually receptive female without mating did not induce CPP. In the female vole, mating until one ejaculation, social cohabitation with mating, or exposure to a male without physical interaction for 6h did not induce CPP. To evaluate whether the rewarding state in males is opioid dependent, the antagonist naloxone was injected i.p. The administration of naloxone blocked the rewarding state induced by one ejaculation and by social cohabitation with mating. Our results demonstrate that in the prairie vole, on the basis of the CPP in the testing conditions used here, the stimulation received with one ejaculation and the mating conditions that lead to pair bonding formation may be rewarding for males, and this reward state is opioid dependent.


Subject(s)
Arvicolinae/physiology , Conditioning, Operant/physiology , Sexual Behavior, Animal/physiology , Social Behavior , Animals , Copulation/physiology , Female , Grassland , Male , Pair Bond , Reward
7.
Scand J Med Sci Sports ; 28(1): 237-245, 2018 Jan.
Article in English | MEDLINE | ID: mdl-28207979

ABSTRACT

The aim was to compare the epidemiology of injuries between elite male and female football players from the same club. Injuries and individual exposure time in a male team and a female team, both playing in the Spanish first division, were prospectively recorded by the club's medical staff for five seasons (2010-2015) following the FIFA consensus statement. Total, training, and match exposure hours per player-season were 20% higher for men compared to women (P<.01). Total, training, and match injury incidence were 30%-40% higher in men (P≤.04) mainly due to a 4.82 (95% confidence interval [CI] 2.30-10.08) times higher incidence of contusions, as there were no differences in the incidence of muscle and joint/ligament injuries (P≥.44). The total number of absence days was 21% larger in women owing to a 5.36 (95% CI 1.11-25.79) times higher incidence of severe knee and ankle ligament injuries. Hamstring strains and pubalgia cases were 1.93 (95% CI 1.16-3.20) and 11.10 (95% CI 1.48-83.44) times more frequent in men, respectively; whereas quadriceps strains, anterior cruciate ligament ruptures, and ankle syndesmosis injuries were 2.25 (95% CI 1.22-4.17), 4.59 (95% CI 0.93-22.76), and 5.36 (95% CI 1.11-25.79) times more common in women, respectively. In conclusion, prevention strategies should be tailored to the needs of male and female football players, with men more predisposed to hamstring strains and hip/groin injuries, and women to quadriceps strains and severe knee and ankle ligament injuries.


Subject(s)
Athletic Injuries/epidemiology , Sex Factors , Soccer/injuries , Adult , Ankle Injuries/epidemiology , Anterior Cruciate Ligament Injuries/epidemiology , Athletes , Athletic Injuries/classification , Contusions/epidemiology , Female , Hamstring Muscles/injuries , Humans , Incidence , Knee Injuries/epidemiology , Male , Prospective Studies , Spain , Young Adult
8.
World J Microbiol Biotechnol ; 34(3): 38, 2018 Feb 19.
Article in English | MEDLINE | ID: mdl-29460068

ABSTRACT

We evaluated, for the first time, the leishmanicidal potential of decanethiol functionalized silver nanoparticles (AgNps-SCH) on promastigotes and amastigotes of different strains and species of Leishmania: L. mexicana and L. major isolated from different patients suffering from localized cutaneous leishmaniasis (CL) and L. mexicana isolated from a patient suffering from diffuse cutaneous leishmaniasis (DCL). We recorded the kinetics of promastigote growth by daily parasite counting for 5 days, promastigote mobility, parasite reproduction by CFSE staining's protocol and promastigote killing using the propidium iodide assay. We also recorded IC50's of promastigotes and amastigotes, therapeutic index, and cytotoxicity by co-culturing macrophages with AgNps-SCH or sodium stibogluconate (Sb) used as reference drug. We used Sb as a reference drug since it is used as the first line treatment for all different types of leishmaniasis. At concentrations 10,000 times lower than those used with Sb, AgNps-SCH had a remarkable leishmanicidal effect in all tested strains of parasites and there was no toxicity to J774A.1 macrophages since > 85% were viable at the concentrations used. Therapeutic index was about 20,000 fold greater than the corresponding one for Sb treated cells. AgNps-SCH inhibited > 80% promastigote proliferation in all tested parasites. These results demonstrate there is a high leishmanicidal potential of AgNps-SCH at concentrations of 0.04 µM. Although more studies are needed, including in vivo testing of AgNps-SCH against different types of leishmaniasis, they can be considered a potential new treatment alternative.


Subject(s)
Antiprotozoal Agents/pharmacology , Leishmania/drug effects , Metal Nanoparticles/chemistry , Silver/pharmacology , Animals , Antimony Sodium Gluconate/pharmacology , Antiprotozoal Agents/administration & dosage , Cell Proliferation/drug effects , Humans , Inhibitory Concentration 50 , Kinetics , Leishmania/growth & development , Leishmaniasis, Cutaneous/drug therapy , Leishmaniasis, Cutaneous/parasitology , Macrophages/drug effects , Macrophages/parasitology , Mice , Mice, Inbred BALB C , Silver/administration & dosage
10.
Allergol Immunopathol (Madr) ; 44(5): 433-8, 2016.
Article in English | MEDLINE | ID: mdl-27255477

ABSTRACT

BACKGROUND: It has been suggested that polymorphisms of histamine metabolising enzymes can be a risk factor for developing histamine-involving diseases. The aim of the present study is to research the possible association between two functional single nucleotide polymorphisms (SNPs): C314T in the Histamine-N-Methyl Transferase gene and C2029G in the Diamine Oxidase gene, with the severity of allergic rhinitis and the number of allergic diseases, in a group of allergic Mexican children. METHODS: We studied 154 unrelated allergic children. SNPs were analysed by RT-PCR. The total serum IgE was measured by chemiluminescence and the serum histamine by ELISA. We used logistic regression analysis to determine OR. RESULTS: Patients carrying the mutant allele for any SNP had more risk to develop higher rhinitis severity or a bigger number of allergic diseases. Haplotype analysis revealed that this effect is synergistic. In patients carrying one or two mutant alleles, serum histamine levels were higher than those of patients carrying only wild alleles. Serum IgE levels were not associated with the presence of mutant alleles. CONCLUSION: The presence of these SNPs in patients with allergic rhinitis can lead to higher serum histamine, therefore to a higher risk of developing more severe symptoms or more associated allergic diseases, even if the serum IgE remains low.


Subject(s)
Amine Oxidase (Copper-Containing)/genetics , Histamine N-Methyltransferase/genetics , Rhinitis, Allergic/genetics , Child , Child, Preschool , DNA Mutational Analysis , Disease Progression , Female , Gene Frequency , Genetic Association Studies , Genetic Predisposition to Disease , Genotype , Histamine/blood , Humans , Immunoglobulin E/blood , Male , Mexico , Polymorphism, Single Nucleotide
11.
Genet Mol Res ; 15(2)2016 May 13.
Article in English | MEDLINE | ID: mdl-27323045

ABSTRACT

Cellular automata model identification is an important way of building simplified simulation models. In this study, we describe a generic architectural framework to ease the development process of new metaheuristic-based algorithms for cellular automata model identification in protein-folding trajectories. Our framework was developed by a methodology based on design patterns that allow an improved experience for new algorithms development. The usefulness of the proposed framework is demonstrated by the implementation of four algorithms, able to obtain extremely precise cellular automata models of the protein-folding process with a protein contact map representation. Dynamic rules obtained by the proposed approach are discussed, and future use for the new tool is outlined.


Subject(s)
Data Mining/methods , Models, Chemical , Protein Folding , Proteins/chemistry , Algorithms , Computer Simulation , Molecular Dynamics Simulation
12.
Enferm Intensiva ; 27(4): 155-167, 2016.
Article in Spanish | MEDLINE | ID: mdl-26803376

ABSTRACT

INTRODUCTION: Safe analgesia and sedation strategies are necessary in order to avoid under or over sedation, as well as improving the comfort and safety of critical care patients. OBJECTIVES: To compare and contrast a multidisciplinary protocol of systematic evaluation and management of analgesia and sedation in a group of critical care patients on mechanical ventilation with the usual procedures. MATERIALS AND METHODS: A cohort study with contemporary series was conducted in a tertiary care medical-surgical ICU February to November during 2013 and 2014. The inclusion criteria were mechanical ventilation ≥ 24h and use of sedation by continuous infusion. Sedation was monitored using the Richmond agitation-sedation scale or bispectral index, and analgesia were measured using the numeric rating scale, or behavioural indicators of pain scale. The study variables included; mechanical ventilation time, weaning time, ventilation support time, artificial airway time, continuous sedative infusion time, daily dose and frequency of analgesic and sedative drug use, hospital stay, and ICU and hospital mortality, Richmond agitation-sedation scale, bispectral index, numeric rating scale, and behavioural indicators of pain scale measurements. Kruskal Wallis and Chi2, and a significance of p<.05 were used. RESULTS: The study included 153 admissions, 75 pre-intervention and 78 post-intervention, with a mean age of 55.7±13 years old, and 67% men. Both groups showed similarities in age, reason for admission, and APACHE. There were non-significant decreases in mechanical ventilation time 4 (1.4-9.2) and 3.2 (1.4-8.1) days, respectively; p= 0.7, continuous sedative infusion time 6 (3-11) and 5 (3-11) days; p= 0.9, length of hospital stay 29 (18-52); 25 (14-41) days; p= 0.1, ICU mortality (8 vs. 5%; p= 0.4), and hospital mortality (10.6 vs. 9.4%: p= 0.8). Daily doses of midazolam and remifentanil decreased 347 (227-479) mg/day; 261 (159-358) mg/day; p= 0.02 and 2175 (1427-3285) mcg/day; 1500 (715-2740) mcg/day; p= 0.02, respectively. There were increases in the use of remifentanil (32% vs. 51%; p= 0.01), dexmedetomidine (0 vs.6%; p= 0.02), dexketoprofen (60 vs. 76%; p= 0.03), and haloperidol (15 vs.28%; p= 0.04). The use of morphine decreased (71 vs. 54%; p= 0.03). There was an increase in the number of measurements and Richmond agitation-sedation scale scores 6 (3-17); 21 (9-39); p< 0.0001, behavioural indicators of pain scale 6 (3-18); 19(8-33); p< 0.001 and numeric rating scale 4 (2-6); 8 (6-17); p< 0.0001. CONCLUSIONS: The implementation of a multidisciplinary protocol of systematic evaluation of analgesia and sedation management achieved an improvement in monitoring and adequacy of dose to patient needs, leading to improved outcomes.


Subject(s)
Analgesia , Conscious Sedation , Deep Sedation , Respiration, Artificial , Cohort Studies , Critical Illness , Female , Humans , Male , Middle Aged , Prospective Studies , Retrospective Studies , Treatment Outcome
13.
Allergy ; 70(8): 1024-7, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25952012

ABSTRACT

Food allergy is recognized as a major public health issue, especially in early childhood. It has been hypothesized that early sensitization to food allergens maybe due to their ingestion as components dissolved in the milk during the breastfeeding, explaining reaction to a food, which has never been taken before. Thus, the aim of this work has been to detect the presence of the food allergens in breast milk by microarray technology. We produced a homemade microarray with antibodies produced against major food allergens. The antibody microarray was incubated with breast milk from 14 women collected from Fundación Jiménez Díaz Hospital. In this way, we demonstrated the presence of major foods allergens in breast milk. The analysis of allergens presented in breast milk could be a useful tool in allergy prevention and could provide us a key data on the role of this feeding in tolerance induction or sensitization in children.


Subject(s)
Allergens/immunology , Breast Feeding/adverse effects , Milk Hypersensitivity/diagnosis , Milk, Human/immunology , Age Factors , Allergens/analysis , Child , Child, Preschool , Female , Food Hypersensitivity/diagnosis , Food Hypersensitivity/immunology , Humans , Incidence , Infant , Male , Milk Hypersensitivity/epidemiology , Milk Hypersensitivity/immunology , Risk Assessment , Sensitivity and Specificity , Sex Factors
14.
Mol Ther ; 21(8): 1579-91, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23732989

ABSTRACT

Cell therapy in animal models of Parkinson's disease (PD) is effective after intrastriatal grafting of dopamine (DA) neurons, whereas intranigral transplantation of dopaminergic cells does not cause consistent behavioral recovery. One strategy to promote axonal growth of dopaminergic neurons from the substantia nigra (SN) to the striatum is degradation of inhibitory components such as chondroitin sulphate proteoglycans (CSPG). An alternative is the guidance of DA axons by chemotropic agents. Semaphorins 3A and 3C enhance axonal growth of embryonic stem (ES) cell-derived dopaminergic neurons in vitro, while Semaphorin 3C also attracts them. We asked whether intranigral transplantation of DA neurons, combined with either degradation of CSPG or with grafts of Semaphorin 3-expressing cells, towards the striatum, is effective in establishing a new nigrostriatal dopaminergic pathway in rats with unilateral depletion of DA neurons. We found depolarization-induced DA release in dorsal striatum, DA axonal projections from SN to striatum, and concomitant behavioral improvement in Semaphorin 3-treated animals. These effects were absent in animals that received intranigral transplants combined with Chondroitinase ABC treatment, although partial degradation of CSPG was observed. These results are evidence that Semaphorin 3-directed long-distance axonal growth of dopaminergic neurons, resulting in behavioral improvement, is possible in adult diseased brains.


Subject(s)
Axons/metabolism , Cell- and Tissue-Based Therapy , Dopaminergic Neurons/metabolism , Dopaminergic Neurons/transplantation , Parkinsonian Disorders/metabolism , Parkinsonian Disorders/therapy , Semaphorins/metabolism , Animals , Cell Differentiation , Cell Line , Corpus Striatum/metabolism , Embryonic Stem Cells/cytology , Embryonic Stem Cells/metabolism , Female , HEK293 Cells/metabolism , HEK293 Cells/transplantation , Humans , Mice , Oxidopamine/metabolism , Parkinsonian Disorders/physiopathology , Rats , Rotarod Performance Test , Semaphorins/genetics , Substantia Nigra , Synaptic Transmission , Transfection
16.
Horm Behav ; 64(1): 70-80, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23673371

ABSTRACT

Non-copulating (NC) males are those animals that do not mate in spite of repeated testing with sexually receptive females. They have been observed in several species including rats and mice. The present experiment was designed to perform a detailed behavioral characterization of NC male mice. Thus, we evaluated their sexual incentive motivation for a sexually receptive female or a sexually active male, olfactory preference for volatile and non-volatile odors from females or males, and olfactory discrimination between female and male volatile odors and food related odors (milk versus vinegar). We compared the activity of the accessory olfactory system (AOS) in copulating (C) and NC males in response to estrous bedding using the induction of Fos-immunoreactivity (Fos-IR) as a measure of neuronal activation. We also determined if estradiol or dopamine treatment could induce sexual behavior in NC males. Finally, we compared the testis weight and the number of penile spines in C, NC, and gonadectomized males. In the sexual incentive motivation test C males spend significantly more time in the female incentive zone than in the male incentive zone. On the other hand, NC males spend the same amount of time in both incentive zones. In tests of olfactory preference, NC males spent less time investigating estrous odors than C males. As well, NC males discriminate urine from conspecifics but they spend less time smelling these odors than C males. In addition, no increase in Fos expression is observed in NC males when they are exposed to odors from estrous females. Our data also suggest that the deficits observed in NC males are not due to lower circulating levels of gonadal hormones, because estradiol supplementation does not induce sexual behavior in these animals, and their testis weight and the number of penile spines are normal. The results suggest that NC males are not sexually motivated by the receptive females and their odors.


Subject(s)
Behavior, Animal/physiology , Copulation/physiology , 2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine/pharmacology , Animals , Discrimination, Psychological/physiology , Dopamine/pharmacology , Dopamine Agonists/pharmacology , Estradiol/pharmacology , Estrous Cycle/physiology , Female , Gene Expression/physiology , Genes, fos , Immunohistochemistry , Male , Mice , Mice, Inbred C57BL , Motivation , Neurons/metabolism , Olfactory Bulb/physiology , Organ Size/physiology , Penis/growth & development , Penis/physiology , Sexual Behavior, Animal/physiology , Smell/physiology , Testis/growth & development , Testis/physiology
17.
Neurologia (Engl Ed) ; 38(9): 681-694, 2023.
Article in English | MEDLINE | ID: mdl-37858889

ABSTRACT

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease among adults worldwide. It is characterised by the death of dopaminergic neurons in the substantia nigra pars compacta and, in some cases, presence of intracytoplasmic inclusions of α-synuclein, called Lewy bodies, a pathognomonic sign of the disease. Clinical diagnosis of PD is based on the presence of motor alterations. The treatments currently available have no neuroprotective effect. The exact causes of PD are poorly understood. Therefore, more precise preclinical models have been developed in recent years that use induced pluripotent stem cells (iPSC). In vitro studies can provide new information on PD pathogenesis and may help to identify new therapeutic targets or to develop new drugs.


Subject(s)
Induced Pluripotent Stem Cells , Neurodegenerative Diseases , Neuroprotective Agents , Parkinson Disease , Adult , Humans , Parkinson Disease/drug therapy , Induced Pluripotent Stem Cells/pathology , Dopaminergic Neurons , Neuroprotective Agents/pharmacology
18.
ESMO Open ; 8(4): 101611, 2023 08.
Article in English | MEDLINE | ID: mdl-37516059

ABSTRACT

BACKGROUND: In the advanced urothelial carcinoma (aUC) scenario there are no consistent immune checkpoint blockade predictive biomarkers. Recently a novel pan-tumor molecular tissue-based biomarker, the Immunotherapy Response Score (IRS), has been proposed. We conducted a retrospective study to validate the prognostic/predictive utility of the IRS in patients with aUC under atezolizumab monotherapy and to characterize its underlying molecular/immune features in the context of the IMvigor210 phase II trial. PATIENTS AND METHODS: This is a post hoc pooled analysis of 261 patients with available clinical, molecular, and immune tumor data treated with atezolizumab monotherapy in the IMvigor210 phase II clinical trial. Efficacy endpoints were overall survival (OS), disease control rate (DCR), and overall response rate (ORR). Survival estimates were calculated by the Kaplan-Meier method, and groups were compared with the log-rank test. The Cox proportional hazards regression model was used to evaluate factors independently associated with OS. Factors associated with disease control (DC) and response were tested with logistic regression in univariable and multivariable analyses. Comparisons between patient and disease characteristics were carried out using chi-square or Fisher's exact tests. All P values were two-sided, and those <0.05 were considered statistically significant. RESULTS: High IRS was significantly associated with a better OS in univariable [hazard ratio (HR) = 0.49, P < 0.001] and multivariable (HR = 0.60, P = 0.018) analyses. DCR and ORR were significantly higher among high IRS patients (DCR for high IRS versus low IRS patients: 57% versus 32%, P < 0.001; ORR: 42% versus 10%, P < 0.001). High IRS patients presented a higher probability of DC and response in univariable [DC: odds ratio (OR) = 2.72, P < 0.001; response: OR = 3.92, P < 0.001] and multivariable (DC: OR = 2.72, P < 0.001; response: OR = 3.92, P < 0.001) analyses. CONCLUSIONS: This study validates IRS as a strong independent prognostic and predictive biomarker for OS and DC/response in patients with aUC treated with atezolizumab monotherapy in the IMvigor210 phase II clinical trial.


Subject(s)
Carcinoma, Transitional Cell , Urinary Bladder Neoplasms , Humans , Carcinoma, Transitional Cell/drug therapy , Retrospective Studies , Biomarkers, Tumor , Immunotherapy/methods
19.
Water Sci Technol ; 65(2): 214-20, 2012.
Article in English | MEDLINE | ID: mdl-22233897

ABSTRACT

Many drivers tend to foster the development of renewable energy production in wastewater treatment plants as many expectations rely upon energy recovery from sewage sludge, for example through biogas use. This paper is focused on the assessment of grease waste (GW) as an adequate substrate for co-digestion with municipal sludge, as it has a methane potential of 479-710 LCH(4)/kg VS, as well as the evaluation of disintegration technologies as a method to optimize the co-digestion process. With this objective three different pre-treatments have been selected for evaluation: thermal hydrolysis, ultrasound and enzymatic treatment. Results have shown that co-digestion processes without pre-treatment had a maximum increment of 128% of the volumetric methane productivity when GW addition was 23% inlet (at 20 days of HRT and with an OLR of 3.0 kg COD/m(3)d), compared with conventional digestion of sewage sludge alone. Concerning the application of the selected disintegration technologies, all pre-treatments showed improvements in terms of methane yield (51.8, 89.5 and 57.6% more for thermal hydrolysis, ultrasound and enzymatic treatment, respectively, compared with non-pretreated wastes), thermal hydrolysis of GW and secondary sludge being the best configuration as it improved the solubilization of the organic matter and the hydrodynamic characteristics of digestates.


Subject(s)
Sewage , Waste Disposal, Fluid/methods , Anaerobiosis , Bacteria, Anaerobic/metabolism , Biological Oxygen Demand Analysis , Bioreactors , Fatty Acids, Volatile/metabolism , Hot Temperature , Hydrolysis , Lipase/chemistry , Methane/metabolism , Renewable Energy , Ultrasonics
20.
Transplant Proc ; 54(9): 2443-2445, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36328815

ABSTRACT

BACKGROUND: Protocol kidney biopsy (PKB) in kidney transplant is a useful tool for graft monitoring because the subclinical detection of histologic lesions helps to modulate immunosuppression. We analyze our experience. METHODS: We performed a descriptive study that analyzed the PKB results at the fourth to sixth month and the first year post transplant of patients with kidney transplant followed in our hospital between January 2015 and June 2021. RESULTS: A total of 100 patients and 134 biopsy results were included, of which 71 were obtained between the fourth and sixth month and 63 at the first year. The mean age was 57.8 years, and 66% were men. Unknown etiology was the most common underlying kidney disease (31%), followed by diabetes mellitus (15%) and polycystic kidney disease (14%). A total of 80% had panel-reactive antibody < 50%. Induction therapy consisted of thymoglobulin (51%) and basiliximab (49%), and maintenance therapy consisted of corticosteroids and tacrolimus (100%), mycophenolate mofetil (82%), and mammalian target of rapamycin inhibitor (18%). Of the total of the PKB results (n = 134), 19 episodes of subclinical rejection (14%) and 10 with borderline changes (7.4%) were observed. Regarding other findings, there were cases of nephrocalcinosis (4.4%), immunoglobulin A nephropathy (2.2%), and BK nephropathy (1.5%). The PKB brought about a change in the therapeutic attitude in 45 cases (33%) of the total number of biopsies, the most frequent change being the administration of boluses of methylprednisolone (12.6%) and the change to mammalian target of rapamycin inhibitor (8.9%). CONCLUSIONS: In our experience, PKB is a useful tool for monitoring and evaluating histologic changes without clinical expression in the kidney graft, allowing us to adapt the treatment during the first year of kidney transplant.


Subject(s)
Kidney Diseases , Kidney Transplantation , Male , Humans , Middle Aged , Female , Kidney Transplantation/adverse effects , Graft Rejection , Immunosuppressive Agents/therapeutic use , Tacrolimus/therapeutic use , Mycophenolic Acid/therapeutic use , Kidney/pathology , Kidney Diseases/pathology , Biopsy , Sirolimus , TOR Serine-Threonine Kinases
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