Integrating Proteomics and Metabolomics Approaches to Elucidate the Mechanism of Responses to Combined Stress in the Bell Pepper (Capsicum annuum).

Bell pepper plants are sensitive to environmental changes and are significantly affected by abiotic factors such as UV-B radiation and cold, which reduce their yield and production. Various approaches, including omics data integration, have been employed to understand the mechanisms by which this crop copes with abiotic stress. This study aimed to find metabolic changes in bell pepper stems caused by UV-B radiation and cold by integrating omic data. Proteome and metabolome profiles were generated using liquid chromatography coupled with mass spectrometry, and data integration was performed in the plant metabolic pathway database. The combined stress of UV-B and cold induced the accumulation of proteins related to photosynthesis, mitochondrial electron transport, and a response to a stimulus. Further, the production of flavonoids and their glycosides, as well as affecting carbon metabolism, tetrapyrrole, and scopolamine pathways, were identified. We have made the first metabolic regulatory network map showing how bell pepper stems respond to cold and UV-B stress. We did this by looking at changes in proteins and metabolites that help with respiration, photosynthesis, and the buildup of photoprotective and antioxidant compounds.

Transcriptomic analysis of bell pepper (Capsicum annuum L.) revealing key mechanisms in response to low temperature stress.

BACKGROUND: Bell pepper (Capsicum annuum L.) is one of the most economically and nutritionally important vegetables worldwide. However, its production can be affected by various abiotic stresses, such as low temperature. This causes various biochemical, morphological and molecular changes affecting membrane lipid composition, photosynthetic pigments, accumulation of free sugars and proline, secondary metabolism, as well as a change in gene expression. However, the mechanism of molecular response to this type of stress has not yet been elucidated. METHODS AND RESULTS: To further investigate the response mechanism to this abiotic stress, we performed an RNA-Seq transcriptomic analysis to obtain the transcriptomic profile of Capsicum annuum exposed to low temperature stress, where libraries were constructed from reads of control and low temperature stress samples, varying on average per treatment from 22,952,190.5-27,305,327 paired reads ranging in size from 30 to 150 bp. The number of differentially expressed genes (DEGs) for each treatment was 388, 417 and 664 at T-17 h, T-22 h and T-41 h, respectively, identifying 58 up-regulated genes and 169 down-regulated genes shared among the three exposure times. Likewise, 23 DEGs encoding TFs were identified at T-17 h, 30 DEGs at T-22 h and 47 DEGs at T-42 h, respectively. GO analysis revealed that DEGs were involved in catalytic activity, response to temperature stimulus, oxidoreductase activity, stress response, phosphate ion transport and response to abscisic acid. KEGG pathway analysis identified that DEGs were related to flavonoid biosynthesis, alkaloid biosynthesis and plant circadian rhythm pathways in the case of up-regulated genes, while in the case of down-regulated genes, they pertained to MAPK signaling and plant hormone signal transduction pathways, present at all the three time points of low temperature exposure. Validation of the transcriptomic method was performed by evaluation of five DEGs by quantitative polymerase chain reaction (q-PCR). CONCLUSIONS: The data obtained in the present study provide new insights into the transcriptome profiles of Capsicum annuum stem in response to low temperature stress. The data generated may be useful for the identification of key candidate genes and molecular mechanisms involved in response to this type of stress.

Validation of Automated Screening for Referable Diabetic Retinopathy With an Autonomous Diagnostic Artificial Intelligence System in a Spanish Population.

PURPOSE: The purpose of this study is to compare the diagnostic performance of an autonomous artificial intelligence (AI) system for the diagnosis of referable diabetic retinopathy (RDR) to manual grading by Spanish ophthalmologists. METHODS: Subjects with type 1 and 2 diabetes participated in a diabetic retinopathy (DR) screening program in 2011 to 2012 in Valencia (Spain), and two images per eye were collected according to their standard protocol. Mydriatic drops were used in all patients. Retinal images-one disc and one fovea centered-were obtained under the Medical Research Ethics Committee approval and de-identified. Exams were graded by the autonomous AI system (IDx-DR, Coralville, Iowa, United States), and manually by masked ophthalmologists using adjudication. The outputs of the AI system and manual adjudicated grading were compared using sensitivity and specificity for diagnosis of both RDR and vision-threatening diabetic retinopathy (VTDR). RESULTS: A total of 2680 subjects were included in the study. According to manual grading, prevalence of RDR was 111/2680 (4.14%) and of VTDR was 69/2680 (2.57%). Against manual grading, the AI system had a 100% (95% confidence interval [CI]: 97%-100%) sensitivity and 81.82% (95% CI: 80%-83%) specificity for RDR, and a 100% (95% CI: 95%-100%) sensitivity and 94.64% (95% CI: 94%-95%) specificity for VTDR. CONCLUSION: Compared to manual grading by ophthalmologists, the autonomous diagnostic AI system had high sensitivity (100%) and specificity (82%) for diagnosing RDR and macular edema in people with diabetes in a screening program. Because of its immediate, point of care diagnosis, autonomous diagnostic AI has the potential to increase the accessibility of RDR screening in primary care settings.

Use in clinical practice of an automated screening method of diabetic retinopathy that can be derived using a diagnostic artificial intelligence system. / Uso en la práctica clínica, de un método de cribado automatizado de retinopatía diabética derivable mediante un sistema de inteligencia artificial de diagnóstico.

BACKGROUND AND OBJECTIVE: To compare the diagnostic performance of an autonomous diagnostic artificial intelligence (AI) system for the diagnosis of derivable diabetic retinopathy (RDR) with manual classification. MATERIALS AND METHODS: Patients with type 1 and type 2 diabetes participated in a diabetic retinopathy (DR) screening program between 2011-2012. 2 images of each eye were collected. Unidentifiable retinal images were obtained, one centered on the disc and one on the fovea. The exams were classified with the autonomous AI system and manually by anonymous ophthalmologists. The results of the AI system and manual classification were compared in terms of sensitivity and specificity for the diagnosis of both (RDR) and diabetic retinopathy with decreased vision (VTDR). RESULTS: 10,257 retinal inages of 5,630 eyes of 2,680 subjects were included. According to the manual classification, the prevalence of RDR was 4.14% and that of VTDR 2.57%. The AI system recorded 100% (95% CI: 97-100%) sensitivity and 81.82% (95% CI: 80 -83%) specificity for RDR, and 100% (95% CI: 95-100%) of sensitivity and 94.64% (95% CI: 94-95%) of specificity for VTDR. CONCLUSIONS: Compared to the manual classification, the autonomous diagnostic AI system registered a high sensitivity (100%) and specificity (82%) in the diagnosis of RDR and macular edema in people with diabetes. Due to its immediate diagnosis, the autonomous diagnostic AI system can increase the accessibility of RDR screening in primary care settings.

Cross-Face Nerve Grafting versus Masseteric-to-Facial Nerve Transposition for Reanimation of Incomplete Facial Paralysis: A Comparative Study Using the FACIAL CLIMA Evaluating System.

BACKGROUND: Incomplete facial paralysis is still a challenge because we must restore what is missing without causing damage to what has recovered. The current literature is insufficient, with a small number of cases. The use of nerve transfers has gained recent popularity for reanimating facial palsy. The authors present a comparative study between cross-face nerve grafting and masseteric-to-facial nerve transposition for incomplete facial paralysis. METHODS: Twenty-eight patients with incomplete unilateral facial paralysis were reanimated with either cross-face nerve grafting (group I, n = 10) or masseteric nerve transfer (group II, n = 18). Commissural displacement and commissural contraction velocity were measured using the FACIAL CLIMA dystem. Spontaneity of the movement and satisfaction were also assessed. RESULTS: When comparing the reconstructed and the healthy sides, statistical differences were found in group I but not in group II, suggesting that the resulting movement was symmetrical in group II but not in group I. Intergroup comparison showed that both commissural displacement and commissural contraction velocity were higher in group II. Spontaneity in group I was higher than in group II, but patients in group II showed more satisfaction, both without being statistically significant. CONCLUSIONS: Reanimation of incomplete facial paralysis can be satisfactorily achieved with both cross-face nerve grafting and direct masseteric-to-facial nerve transposition. However, with the masseteric nerve, better symmetry, a higher degree of recovery, and an increased level of satisfaction are achieved in a one-stage operation. Furthermore, both nerve sources are able to restore spontaneity in more than 50 percent of the patient's daily life, with no significant differences between them. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

A Predictable Approach for Osteotomy in Rhinoplasty: A New Concept of Open External Osteotomy.

Nasal osteotomies are a cornerstone step for closing an open roof deformity after dorsal hump surgery. Notwithstanding, the optimal method of nasal osteotomy remains controversial, as evidenced by the variety of approaches with no consensus between authors. Moreover, the election of the technique responds to surgeon's preference. We proposed a new way to perform both medial and lateral osteotomies under direct vision. Direct vision of nasal osteotomies provides more predictable control and precision than blind procedures, making this procedure more reliable and easier for both novel and experienced surgeons. Other advantages include conservation of nasal muscle, angular vasculature, and periosteum, which allow less postoperative ecchymosis and edema and less risk of synechia and lacrimal sac injury.

[Allergic hypersensitivity to antiretroviral drugs: etravirine, raltegravir and darunavir]. / Hipersensibilidad alérgica a antirretrovirales: etravirina, raltegravir y darunavir.

All antiretroviral drugs can have both short-term and long-term adverse events. The risk of specific side effects varies from drug to drug, from drug class to drug class, and from patient to patient. A better understanding of the adverse effects of antiretroviral agents is of interest not only for HIV specialists, but also for other physicians who care allergy reactions in HIV-positive patients. Each antiretroviral medication is associated with its own specific adverse effects or may cause problems only in particular circumstances. In this article some adverse allergic effects of HAART therapy in the treatment of HIV from a patient are reviewed. Our aim is to gain a working knowledge of these adverse effects, promoting the early recognition and reversal of potentially serious adverse effects, and reducing the potential for adverse drug interactions.

Todos los fármacos antirretrovirales tienen efectos adversos que pueden manifestarse a corto o largo plazo. El riesgo de efectos secundarios específicos varía de un fármaco a otro, de una clase de medicamento a otra y de un paciente a otro. Una mejor comprensión de estos efectos es de interés no sólo para los especialistas en VIH, sino también para otros médicos que atendemos las reacciones alérgicas en los pacientes VIH-positivos. Cada fármaco antirretroviral se asocia con sus propios efectos adversos específicos o puede causar problemas sólo en circunstancias particulares. En este artículo se revisan algunos efectos alérgicos adversos del tratamiento antirretroviral de gran actividad (TARGA) en el tratamiento del VIH de un paciente. Nuestro objetivo es obtener un conocimiento práctico de estos efectos adversos, promoviendo el reconocimiento temprano y la reversión de los efectos adversos graves y reducir las interacciones farmacológicas adversas.

[Cutaneous necrotic loxoscelism. A case report]. / Loxoscelismo cutáneo necrótico. Informe de un caso.

Brown recluse (Loxosceles spp.) spiders are arachnid species known to cause necrotic arachnidism. The envenomation, described as loxoscelism, is associated with localized pain, erythema, and edema followed by the development of necrosis. However, the specific pathophysiological mechanisms by which Loxosceles venom exerts these noxious symptoms are multifactorial and not fully understood. The causative factor for production of necrotic lesions is generally considered to be the enzyme sphingomyelinase D (SMD), which cleaves sphingomyelin to form choline and ceramide 1-phosphate. Four active forms of SMD with molecular weight of 32 000 are found in L recluse. Sphingomyelinases of comparable size are also described in the venoms of Loxosceles intermedia, gaucho and laeta. Here we describe the case of a young male adult who suffered a spider bite on his left forearm which evolved into a necrotic lesion, and after a few days the injury healed completely. One week later the patient developed two similar lesions on his left leg. The diagnosis was established by clinical data and by biopsy findings. The patient did not developed systemic complications.

[Hypersensitivity to metals in patients with orthopedic implants]. / Hipersensibilidad a metales en pacientes con implantes ortopédicos.

All metals in contact with biological systems suffer corrosion, which is an electrochemical process that causes metallic ions formation, known as haptens, which link with endogenous or exogenous proteins, therefore inducing an immune response. A hypersensitivity response to an implanted material should be suspected when cutaneous lesions or inflammatory reactions occur proximal to or surrounding the site of the metallic orthopedic implant. At present there is no a reliable diagnostic test for the determination of hypersensitivity to implanted metallic devices. It has been shown that the products of corrosive degradation are associated with dermatitis, urticaria and vasculitis. Cutaneous lesions in patients with unsuccessful metallic implants are more frequent than in non-rejected implants or the general population. Although the cellular and humoral hypersensitivity response in metallic orthopedic implants has been clearly identified, the risk is very low. Nowadays the importance of hypersensitivity to metals as a contributing factor in the failure of implants is unknown.

[Immunology and BCG therapeutics]. / Inmunología y terapéutica de la vacuna BCG.

The importance in the study of bacillus of Calmette-Guérin or BCG is related to several functions derived from its influence on the immunological system, between which it is found the prevention of the dissemination of the tubercular bacillus, its utilization as immunomodulator in some oncologic illness (as vesical cancer) in order to avoid post-surgical recidiva or in some forms of immunotherapy, as the cytokine (interferon alpha and interleukin-2); in addition, BCG vaccine is supplied like an immunomodulator in treatment of melanoma. It is important to continue with the study of the BCG strains for its great utility in the treatment of various diseases, example of the previous is the Tice strain, which is used in the superficial cancer of bladder and in the production of new and more powerful vaccines for the protection of tuberculosis.

[Effects of methimazole on the evolution of the allergic rhinitis of patients with Graves' disease]. / Efectos del metimazol en la evolución de la rinitis alérgica en pacientes con enfermedad de Graves.

BACKGROUND: The methimazole has long been used for treating Graves' disease to decrease thyroid hormone production and obtain a thyroid normofunction, but this drug has also immunosuppressive and immunomodulation effects. OBJECTIVE: To analyze in patients with Graves' disease treated with methimazole and allergic rhinitis, the clinical evolution of the allergic rhinitis with the immunosuppressive and immunomodulation effects of the methimazole. PATIENTS AND METHODS: A comparative and observational study was done in the Mexico's General Hospital, in twenty-six patients with Graves' disease treated with methimazole 10 mg, thyroid profile was done, and when subjects obtained a thyroid normofunction continued with the same doses of methimazole and received also 12.5 mcg/day of levothyroxine. All the patients were diagnosed with allergic rhinitis, and they were divided into two groups (11 females and 2 males each). Both groups continued with the same treatment of methimazole and levothyroxine, but group II was given also antihistamines H1 of second-generation (loratadine) daily, and specific immunotherapy during six months. We described and compared the clinical evolution of the allergic rhinitis of the two groups with the treatment. RESULTS: In the group I, changes in the clinical evolution of the allergic rhinitis after six months were not observed. In the group II, by week 10 the symptoms of the allergic rhinitis were controlled in 80% of the patients, and by week 14 all the patients of this group were asymptomatic. CONCLUSIONS: In patients with allergic rhinitis and Graves' diseases with methimazole-thyroid normofunction we observed that there is not influence of methimazole on clinical evolution of the allergic rhinitis.

[Peripheral anticholinergic syndrome]. / Sindrome anticolinérgico periférico.

This is a case report of a woman of 38 years old, studied and analyzed at the service of allergy and immunology with clinical manifestations of allergic rhinitis; studies of laboratory, cabinet and intradermal test were made to corroborate this diagnosis and the treatment with specific hyposensitization, oral antihistaminines and inhaled steroids was started. Two years later the patient referred urinary retention without important antecedents, so, a peripheral anticholinergic syndrome (PAS) was suspected, a urodynamic test study was carried out consisting in a uroflujometry, static and dynamic urethral profile, cystometry, flow pressure study and electromyography, which diagnosed low urinary obstruction (functional) and vesical sphincter pseudodysfunction, demonstrating the PAS associated with oral antihistamines.

[Allergy and neurotoxicity induced by bee sting. Case report and literature review]. / Alergia y neurotoxicidad inducida por piquete de abeja. Reporte de un caso y revisión bibliográfica.

Under the heading of this subject we deal with stings by arthropods, making of bees, commenting on the composition of the poisons and the different local and general reactions that are differences that exist between the stings The venom contains many biologically active components such as melitin, phospholipase A2, apamin, mast cell degranulation peptide, hyaluronidase, histamine, and dopamine. That neurotoxic venom secretory phospholipases A2 (sPLA2) have specific receptors in brain membranes called N-type receptors that are likely to play a role in the molecular events leading to neurotoxicity of these proteins. The sPLA2 found in honeybee venom is neurotoxic and binds to this receptor with high affinity. Poneratoxin is small neuropeptide found in the venom of arthropod (bee). It is stored in the venom reservoir as a inactive 25 residue peptide. Here we describe both chemically synthesized poneratoxin, insect larvae were paralyzed by injection of either of the purified toxins. These toxins are used in research as molecular probes, targeting with high affinity selected ion channel subtypes. As such, they are very useful for understanding the mechanism of synaptic transmission. Poneratoxin affects the voltage-dependent sodium channels and blocks the synaptic transmission in the insect central nervous system in a concentration-dependent manner; we think that in the human this is same.

Un caso más que dudoso de uveítis anterior relacionada con fármacos / A doubtful case of anterior uveitis drug related

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