Impact of coronary calcium morphology on intravascular lithotripsy.

BACKGROUND: Coronary calcification negatively impacts optimal stenting. Intravascular lithotripsy (IVL) is a new calcium modification technique. AIMS: We aimed to assess the impact of different calcium morphologies on IVL efficacy. METHODS: This was a prospective, multicentre study (13 tertiary referral centres). Optical coherence tomography (OCT) was performed before and after IVL, and after stenting. OCT-defined calcium morphologies were concentric (mean calcium arc >180°) and eccentric (mean calcium arc ≤180°). The primary outcomes were angiographic success (residual stenosis <20%) and the presence of fracture by OCT in concentric versus eccentric lesions. RESULTS: Ninety patients were included with a total of 95 lesions: 47 concentric and 48 eccentric. The median number of pulses was 60 (p=1.00). Following IVL, the presence of fracture was not statistically different between groups (79.0% vs 66.0% for concentric vs eccentric; p=0.165). The number of fractures/lesion (4.2±4.4 vs 2.3±2.8; p=0.018) and ≥3 fractures/lesion (57.1% vs 34.0%; p=0.029) were more common in concentric lesions. Angiographic success was numerically but not statistically higher in the concentric group (87.0% vs 76.6%; p=0.196). By OCT, no differences were noted in final minimum lumen area (5.9±2.2 mm2 vs 6.2±2.1 mm2; p=0.570), minimum stent area (5.9±2.2 mm² vs 6.25±2.4 mm2; p=0.483), minimum stent expansion (80.9±16.7% vs 78.2±19.8%), or stent expansion at the maximum calcium site (100.6±24.2% vs 95.8±27.3%) (p>0.05 for all comparisons of concentric vs eccentric, respectively). Calcified nodules were found in 29.5% of lesions; these were predominantly non-eruptive (57%). At the nodule site, dissection was more common than fracture with stent expansion of 103.6±27.2%. CONCLUSIONS: In this prospective, multicentre study, the effectiveness of IVL followed by stenting was not significantly affected by coronary calcium morphology.

Two-Generation Toxicity Study of the Antioxidant Compound Propyl-Propane Thiosulfonate (PTSO).

Propyl-propane thiosulfonate (PTSO), an antioxidant organosulfur compound present in the genus Allium, has become a potential natural additive for food and feed, as well as a possible biopesticide for pest control in plants. A toxicological assessment is necessary to verify its safety for livestock, consumers, and the environment. As part of the risk assessment of PTSO, this study was designed to explore its potential reproductive toxicity in mice following the OECD 416 guideline. The investigation spans two generations to comprehensively evaluate potential reproductive, teratogenic, and hereditary effects. A total of 80 CD1 mice per sex and generation were subjected to PTSO exposure during three phases (premating, gestation, and lactation). This evaluation encompassed three dose levels: 14, 28, and 55 mg PTSO/kg b.w./day, administered through the feed. No clinical changes or mortality attributed to the administration of PTSO were observed in the study. Some changes in the body weight and food consumption were observed, but not related to sex or in a dose-dependent manner. The two parental generations (F0, F1) exhibited normal reproductive performance, and the offspring (F1 and F2) were born without any abnormalities. The serum sexual hormone levels (progesterone -P-, testosterone -T-, estradiol -E2-, follicular stimulating hormone -FSH-, and luteinizing hormone -LH-) were in a normal range. Although significant changes were observed in the sperm analysis in the case of F0 group, no variation was found for F1 group, and no alterations in fertility were recorded either. The absolute organ weights and relative organ weight/body weight and organ weight/brain weight ratios, and the complete histopathological study, showed no significant alterations in males and females for all the generations considered. Considering all the results obtained, PTSO is not considered a reproductive or developmental toxicant in mice under the assayed conditions. These results support the good safety profile of PTSO for its potential application in the agrifood sector.

Prognostic value of haematological parameters and [18F]FDG PET/CT metabolic parameters in head and neck cancer.

AIM: To determine the usefulness of neutrophil/lymphocyte (N/L) and platelet/lymphocyte (P/L) ratios as well as quantitative [18F]FDG PET/CT parameters as prognostic factors for overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS) in patients with head and neck squamous cell carcinoma (HyN). MATERIAL AND METHODS: Sixty-six patients (56 men) diagnosed with HyN carcinoma were retrospectively assessed over an 8-year interval. Maximum SUV (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis (TLG) parameters were determined from the PET/CT study at diagnosis. After treatment with chemoradiotherapy, patient survival was assessed. The Cox regression model and the Kaplan-Meier method were used to analyse prognostic factors and survival curves. RESULTS: Median follow-up was 50.4 months, with 39 recurrences-progressions and 39 deaths. In the univariate analysis, metabolic parameters, except SUVmax, were predictive factors for all three survivals and the two blood parameters were predictive for OS and EFS. TLG was the only predictive factor in the multivariate analysis. The three survival curves were significantly different for the metabolic parameters and the OS curve for the N/L ratio. Correlations were seen between N/L ratio, MTV and TLG. No correlations were demonstrated between P/L ratio and metabolic parameters. CONCLUSION: The use of haematological and metabolic markers would allow to identify patients with a high risk of recurrences and por survival and to individualise treatment by applying more aggressive therapies.

Genomic Assessment of the Contribution of the Wolbachia Endosymbiont of Eurosta solidaginis to Gall Induction.

We explored the genome of the Wolbachia strain, wEsol, symbiotic with the plant-gall-inducing fly Eurosta solidaginis with the goal of determining if wEsol contributes to gall induction by its insect host. Gall induction by insects has been hypothesized to involve the secretion of the phytohormones cytokinin and auxin and/or proteinaceous effectors to stimulate cell division and growth in the host plant. We sequenced the metagenome of E. solidaginis and wEsol and assembled and annotated the genome of wEsol. The wEsol genome has an assembled length of 1.66 Mbp and contains 1878 protein-coding genes. The wEsol genome is replete with proteins encoded by mobile genetic elements and shows evidence of seven different prophages. We also detected evidence of multiple small insertions of wEsol genes into the genome of the host insect. Our characterization of the genome of wEsol indicates that it is compromised in the synthesis of dimethylallyl pyrophosphate (DMAPP) and S-adenosyl L-methionine (SAM), which are precursors required for the synthesis of cytokinins and methylthiolated cytokinins. wEsol is also incapable of synthesizing tryptophan, and its genome contains no enzymes in any of the known pathways for the synthesis of indole-3-acetic acid (IAA) from tryptophan. wEsol must steal DMAPP and L-methionine from its host and therefore is unlikely to provide cytokinin and auxin to its insect host for use in gall induction. Furthermore, in spite of its large repertoire of predicted Type IV secreted effector proteins, these effectors are more likely to contribute to the acquisition of nutrients and the manipulation of the host's cellular environment to contribute to growth and reproduction of wEsol than to aid E. solidaginis in manipulating its host plant. Combined with earlier work that shows that wEsol is absent from the salivary glands of E. solidaginis, our results suggest that wEsol does not contribute to gall induction by its host.

Coronary Obstruction After Transcatheter Aortic Valve Replacement: Insights From the Spanish TAVI Registry.

BACKGROUND: Coronary obstruction (CO) following transcatheter aortic valve replacement (TAVR) is a life-threatening complication, scarcely studied. OBJECTIVES: The authors analyzed the incidence of CO after TAVR, presentation, management, and in-hospital and 1-year clinical outcomes in a large series of patients undergoing TAVR. METHODS: Patients from the Spanish TAVI (Transcatheter Aortic Valve Implantation) registry who presented with CO in the procedure, during hospitalization or at follow-up were included. Computed tomography (CT) risk factors were assessed. In-hospital, 30-day, and 1-year all-cause mortality rates were analyzed and compared with patients without CO using logistic regression models in the overall cohort and in a propensity score-matched cohort. RESULTS: Of 13,675 patients undergoing TAVR, 115 (0.80%) presented with a CO, mainly during the procedure (83.5%). The incidence of CO was stable throughout the study period (2009-2021), with a median annual rate of 0.8% (range 0.3%-1.3%). Preimplantation CT scans were available in 105 patients (91.3%). A combination of at least 2 CT-based risk factors was less frequent in native than in valve-in-valve patients (31.7% vs 78.3%; P < 0.01). Percutaneous coronary intervention was the treatment of choice in 100 patients (86.9%), with a technical success of 78.0%. In-hospital, 30-day, and 1-year mortality rates were higher in CO patients than in those without CO (37.4% vs 4.1%, 38.3% vs 4.3%, and 39.1% vs 9.1%, respectively; P < 0.001). CONCLUSIONS: In this large, nationwide TAVR registry, CO was a rare, but often fatal, complication that did not decrease over time. The lack of identifiable predisposing factors in a subset of patients and the frequently challenging treatment when established may partly explain these findings.

Identification of in vitro metabolites of an Allium organosulfur compound and environmental toxicity prediction as part of its risk assessment.

Propyl-propane-thiosulfonate (PTSO) is an organosulfur compound found inAllium spp. Due to its antioxidant and antimicrobial activities, PTSO has been proposed for applications in the agri-food sector, such as feed additive. However, its use with commercial purposes depends on its toxicity evaluation. The present work aimed to perform a pilot-study of toxicokinetic profile of PTSO combining in silico and in vitro techniques, important steps in the risk assessment process. In silico ecotoxicity studies were also performed considering the importance of the environmental impact of the compound before its commercial use. First, an analytical method has been developed and validated to determine the original compound and its metabolites by ultra-performance liquid chromatography-tandem mass spectrometry. The phase I and II metabolism of PTSO was predicted using Meta-Pred Web Server. For the phase I metabolism, rat (male and female) and human liver microsomes were incubated with PTSO and NADPH regeneration system. Furthermore, in the phase II, microsomes were incubated with PTSO and glutathione or uridine 5'- diphosphoglucuronic acid. The analysis revealed the presence of propylpropane thiosulfinate (PTS) originated by redox reaction in phase I, and two conjugates from the phase II: S-propylmercaptoglutathione (GSSP) and S-propylmercaptocysteine (CSSP). Additionally, considering the environmental fate of PTSO and its metabolites, the ADME parameters and the potential ecotoxicity were also predicted using in silico softwares. The results of the ecotoxicity in silico study evidenced that the metabolism induced the formation of detoxified metabolites from the parent compound, except for dimercaprol and 3-mercaptopropane1,2-diol. Further in vivo assays are needed to confirm this prediction.

Analytical Platform for the Study of Metabolic Pathway of Propyl Propane Thiosulfonate (PTSO) from Allium spp.

The present work is focused on the development of an analytical platform to elucidate the metabolic pathway of PTSO from onion, an organosulfur compound well-known for its functional and technological properties and its potential application in animal and human nutrition. This analytical platform consisted of the use of gas chromatography-mass spectrometry (GC-MS) and ultra-high performance liquid chromatography quadrupole with time-of-flight MS (UHPLC-Q-TOF-MS) in order to monitor volatile and non-volatile compounds derived from the PTSO. For the extraction of the compounds of interest, two different sample treatments were developed: liquid-liquid extraction (LLE) and salting-out assisted liquid-liquid extraction (SALLE) for GC-MS and UHPLC-Q-TOF-MS analysis, respectively. Once the analytical platform was optimised and validated, an in vivo study was planned to elucidate PTSO metabolisation, revealing the presence of dipropyl disulfide (DPDS) in liver samples with concentrations between 0.11 and 0.61 µg g-1. The DPDS maximum concentration in the liver was observed at 0.5 h after the intake. DPDS was also present in all plasma samples with concentrations between 2.1 and 2.4 µg mL-1. In regard to PTSO, it was only found in plasma at times above 5 h (0.18 µg mL-1). Both PTSO and DPDS were excreted via urine 24 h after ingestion.

Switch to ocrelizumab in MS patients treated with natalizumab in extended interval dosing at high risk of PML: A 96-week follow-up pilot study.

We aimed to assess the long-term safety and effectiveness of ocrelizumab in a cohort of patients with multiple sclerosis (MS) at high risk of progressive multifocal leukoencephalopathy (PML), previously treated with natalizumab in extending interval dosing (EID), who switched to ocrelizumab and to compare them with patients who continued EID-natalizumab. Thirty MS patients previously treated with natalizumab in EID (every 8 weeks) were included in this observational retrospective cohort study. Among them, 17 patients were switched to ocrelizumab and 13 continued with EID-natalizumab. Except for the John Cunningham virus (JCV) index, no significant differences were detected between both groups. Main outcome measures included: annualized relapse rate (ARR), radiological activity, disability progression, and the NEDA-3 index. Patients were followed for 96 weeks. The median washout period in ocrelizumab-switchers was 6 weeks. Among them, AAR and radiological activity during follow-up were 0.03, without significant differences in comparison with the previous period on natalizumab-EID. The comparison between ocrelizumab-switchers and patients continuing on EID-natalizumab showed no significant differences in AAR, radiological activity, or disability progression. However, the proportion of patients maintaining a NEDA-3 status in week 96 was slightly superior among ocrelizumab-switchers (94 vs 69%). No serious adverse events were observed in any group. In conclusion, switching from EID-natalizumab to ocrelizumab can be considered as a therapeutic option, particularly in patients with MS at high risk of PML, to mitigate the risks of both PML and disease reactivation.

Hyperspectral Face Recognition with Adaptive and Parallel SVMs in Partially Hidden Face Scenarios.

Hyperspectral imaging opens up new opportunities for masked face recognition via discrimination of the spectral information obtained by hyperspectral sensors. In this work, we present a novel algorithm to extract facial spectral-features from different regions of interests by performing computer vision techniques over the hyperspectral images, particularly Histogram of Oriented Gradients. We have applied this algorithm over the UWA-HSFD dataset to extract the facial spectral-features and then a set of parallel Support Vector Machines with custom kernels, based on the cosine similarity and Euclidean distance, have been trained on fly to classify unknown subjects/faces according to the distance of the visible facial spectral-features, i.e., the regions that are not concealed by a face mask or scarf. The results draw up an optimal trade-off between recognition accuracy and compression ratio in accordance with the facial regions that are not occluded.

Cirugía radioguiada de paratiroides con 18FCH. Mito o realidad / Radioguided parathyroid surgery with 18FCH. Myth or reality

El hiperparatiroidismo primario (HPTP) es la principal causa de hipercalcemia en pacientes no hospitalizados, estando causado en el 85-90% de los casos por un adenoma solitario. La cirugía radioguiada de paratiroides (CRGP), como técnica GOSTT (Guided intraOperative Scintigraphic Tumor Targeting), utiliza la SPECT-TC con 99mTc-MIBI como técnica de elección. La PET-TC con 18F-Colina (18FCH) puede emplearse en pacientes con 99mTc-MIBI negativo, obteniéndose sensibilidades próximas al 95%. El uso de la 18FCH en la CRGP es muy complejo recomendándose la utilización de otros trazadores como los 99mTc-Macroagregados (99mTc-MAA) o las semillas de Yodo-125 (125I-Semilla). La CRGP disminuye el tiempo quirúrgico, los costes hospitalarios y la morbilidad sobre el paciente, con una elevada efectividad y eficiencia. (AU)

Primary hyperparathyroidism (PHPT) is the main cause of hypercalcemia in non-hospitalized patients, being caused in 85-90% of cases by a solitary adenoma. Radioguided parathyroid surgery (RGPS), as a GOSTT (Guided intraOperative Scintigraphic Tumor Targeting) technique, uses SPECT-TC with 99mTc -MIBI as the technique of choice. PET-TC with 18F-Choline (18FCH) can be used in patients with negative 99mTc-MIBI, obtaining sensitivities close to 95%. The use of 18FCH in CRGP is very complex, recommending the use of other tracers such as 99mTc-Macroaggregates (99mTc-MAA) or Iodine-125 seeds (125I-Seed). RGPS reduces surgical time, hospital costs and patient morbidity, with high effectiveness and efficiency. (AU)

Ammonia-oxidizing archaea possess a wide range of cellular ammonia affinities.

Nitrification, the oxidation of ammonia to nitrate, is an essential process in the biogeochemical nitrogen cycle. The first step of nitrification, ammonia oxidation, is performed by three, often co-occurring guilds of chemolithoautotrophs: ammonia-oxidizing bacteria (AOB), archaea (AOA), and complete ammonia oxidizers (comammox). Substrate kinetics are considered to be a major niche-differentiating factor between these guilds, but few AOA strains have been kinetically characterized. Here, the ammonia oxidation kinetic properties of 12 AOA representing all major cultivated phylogenetic lineages were determined using microrespirometry. Members of the genus Nitrosocosmicus have the lowest affinity for both ammonia and total ammonium of any characterized AOA, and these values are similar to previously determined ammonia and total ammonium affinities of AOB. This contrasts previous assumptions that all AOA possess much higher substrate affinities than their comammox or AOB counterparts. The substrate affinity of ammonia oxidizers correlated with their cell surface area to volume ratios. In addition, kinetic measurements across a range of pH values supports the hypothesis that-like for AOB-ammonia and not ammonium is the substrate for the ammonia monooxygenase enzyme of AOA and comammox. Together, these data will facilitate predictions and interpretation of ammonia oxidizer community structures and provide a robust basis for establishing testable hypotheses on competition between AOB, AOA, and comammox.

Hemoglobina glucosilada en el diagnóstico de diabetes gestacional en mujeres mexicanas durante el tercer trimestre / Glycosylated hemoglobin in the diagnosis of gestational diabetes in Mexican women during the third trimester

Resumen El objetivo del trabajo fue analizar los valores de hemoglobina glucosilada en el tercer trimestre de embarazo como predictores alternativos de la diabetes gestacional en pacientes del Noreste de México. Se trata de un estudio retrospectivo de casos y controles a partir de 121 expedientes de pacientes embarazadas, divididos en dos grupos, pacientes con diabetes gestacional (casos) y gestantes con valores glucémicos normales (controles). Se analizaron los factores de riesgo asociados a la diabetes gestacional y se obtuvo un punto de corte para la hemoglobina glucosilada. Se encontró que la obesidad materna, la edad y el antecedente del padecimiento fueron asociados significativamente con la diabetes gestacional. Valores de hemoglobina glucosilada ≥5% incrementaron el riesgo de padecer diabetes mellitus gestacional 4 veces y, aunado a un factor de riesgo, la probabilidad se incrementó 7 veces. Se concluye que los valores de hemoglobina glucosilada en el tercer trimestre de embarazo podrían emplearse como prueba diagnóstica de la diabetes gestacional en pacientes del Noreste de México. Sin embargo, aunque las diferencias encontradas fueron estadísticamente significativas, los resultados se deben interpretar con cautela y requieren su confirmación con estudios que incluyan una muestra mayor.

Abstract The objective of this study was to analise glycosylated hemoglobin values in the third trimester of pregnancy as an alternative predictor of gestational diabetes in North East Mexican cohort patients. This is a retrospective case-control study based on 121 records of pregnant patients, divided into two groups, patients with gestational diabetes (cases) and pregnant women with normal glycemic values (control). The risk factors associated with gestational diabetes were analised and a cut-off point for glycosylated hemogestaglobin was obtained. It was found that maternal obesity, age and a history of the condition were significantly associated with gestational diabetes. Values of glycosylated hemoglobin ≥5% increased the risk of suffering from gestational diabetes 4 times, and coupled with a risk factor, the risk increased 7 times. It is concluded that glycosylated hemoglobin values in the third trimester of pregnancy could be used as a diagnostic test for gestational diabetes in patients from the North East of Mexico. Although the differences found were statistically significant, our results must be interpreted with caution and require confirmation by studies with a larger sample.

Resumo O objetivo deste estudo foi analisar os valores da hemoglobina glicada no terceiro trimestre de gestação como preditores alternativos do diabetes gestacional em pacientes na região nordeste do México. Trata-se de um estudo retrospectivo de casos e controles utilizando 121 prontuários de gestantes divididas em dois grupos; pacientes com diabetes gestacional (casos) e gestantes com valores de glicemia normais (controles). Foram analisados os fatores de risco associados a diabetes gestacional obtendo-se um ponto de corte para a hemoglobina glicada. Descobriu-se que a obesidade materna, idade e antecedentes da doença foram associados significativamente ao diabetes gestacional. Valores da hemoglobina glicada ≥ 5% aumentaram o risco de padecer diabetes mellitus gestacional 4 vezes, e juntamente a um fator de risco, a probabilidade aumentou 7 vezes. Conclui-se que os valores da hemoglobina glicada no terceiro trimestre de gestação poderiam ser usados como teste diagnóstico do diabetes gestacional em pacientes da região nordeste do México. Embora as diferenças encontradas tenham sido estatisticamente significativas, os resultados devem ser interpretados com cautela e requerem confirmação através de estudos que incluam uma amostra maior.

Simultaneous determination of Allium compounds (Propyl propane thiosulfonate and thiosulfinate) in animal feed using UPLC-MS/MS.

Propyl-propane-thiosulfonate (PTSO) and Propyl-propane-thiosulfinate (PTS) are organosulfur compounds used to supplement the diet of livestock because of their beneficial effects on feed palatability, their antibacterial, anti-inflammatory, and antimethanogenic activities. Besides, antibiotic residues in the environment can be reduced by using these natural bioactive compounds. The objective of this study was to optimize the extraction parameters for the analysis of PTSO and PTS in feed matrices by performing a solid-liquid extraction and quantification by Ultra performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). Optimization was performed using the Response Surface Methodology on a Box-Behnken experimental design, optimizing the following parameters: solvent:sample ratios and evaporation temperature set for the rotary evaporator. The method was validated for 3 concentration levels for both PTSO (100, 500, 1000 ng g-1) and PTS (500, 1150, 2300 ng g-1). The highest recoveries of PTSO and PTS were obtained using 12.5 mL of 100% acetonitrile, stirring for 15 min, and an evaporation temperature of 20 °C. The validated method was further applied to detect and quantify these compounds in different feed matrices. In conclusion, this is the first study to simultaneously analyze PTSO and PTS at low concentrations, employing a sensitive technique such as UPLC-MS/MS.

Feasibility and cost of a telemedicine-based short-term plan for initial access in general dermatology in Andalusia, Spain.

BACKGROUND: In developed countries, health care delivery in dermatology is hampered by the low availability of dermatologists. OBJECTIVE: To analyze the feasibility of a teledermatology-based action plan to provide initial dermatologic care in areas with low availability of dermatologists. METHODS: A cross-sectional study describing the feasibility and cost of a 12-month action plan based on a store-and-forward teledermatology (TD) connecting primary care centers and a TD center. Teleconsultations from patients complaining of any cutaneous condition were included. The primary outcome measure was the percentage of patients not referred to the local dermatologist. RESULTS: Among the total of 15,523 teleconsultations attended in the TD-based action plan, 3360 (21.65%) required a face-to-face visit with a local dermatologist. In 32.32% (n = 5017) of the cases, a therapeutic and follow-up plan report was issued. The most common conditions managed were melanocytic nevi (15.63%, n = 2426), followed by seborrheic keratosis (14.89%, n = 2312), and actinic keratosis (8.65%, n = 1342). The average response time was 14.52 days (95% CI 14.35-15.23). The additional total investment in this action plan was $142,681.01, with a unit cost of 9.20$/patient. LIMITATIONS: Noncontrolled study. CONCLUSIONS: Experienced dermatologists working with store-and-forward TD can deliver a fast and effective response in health care areas with access limitations.

Long-term effects of coronavirus disease 2019 on the cardiovascular system, CV COVID registry: A structured summary of a study protocol.

BACKGROUND: Patients presenting with the coronavirus-2019 disease (COVID-19) may have a high risk of cardiovascular adverse events, including death from cardiovascular causes. The long-term cardiovascular outcomes of these patients are entirely unknown. We aim to perform a registry of patients who have undergone a diagnostic nasopharyngeal swab for SARS-CoV-2 and to determine their long-term cardiovascular outcomes. STUDY AND DESIGN: This is a multicenter, observational, retrospective registry to be conducted at 17 centers in Spain and Italy (ClinicalTrials.gov number: NCT04359927). Consecutive patients older than 18 years, who underwent a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV2 in the participating institutions, will be included since March 2020, to August 2020. Patients will be classified into two groups, according to the results of the RT-PCR: COVID-19 positive or negative. The primary outcome will be cardiovascular mortality at 1 year. The secondary outcomes will be acute myocardial infarction, stroke, heart failure hospitalization, pulmonary embolism, and serious cardiac arrhythmias, at 1 year. Outcomes will be compared between the two groups. Events will be adjudicated by an independent clinical event committee. CONCLUSION: The results of this registry will contribute to a better understanding of the long-term cardiovascular implications of the COVID19.

New short cationic antibacterial peptides. Synthesis, biological activity and mechanism of action.

We report a theoretical and experimental study on a new series of small-sized antibacterial peptides. Synthesis and bioassays for these peptides are reported here. In addition, we evaluated different physicochemical parameters that modulate antimicrobial activity (charge, secondary structure, amphipathicity, hydrophobicity and polarity). We also performed molecular dynamic simulations to assess the interaction between these peptides and their molecular target (the membrane). Biophysical characterization of the peptides was carried out with different techniques, such as circular dichroism (CD), linear dichroism (LD), infrared spectroscopy (IR), dynamic light scattering (DLS), fluorescence spectroscopy and TEM studies using model systems (liposomes) for mammalian and bacterial membranes. The results of this study allow us to draw important conclusions on three different aspects. Theoretical and experimental results indicate that small-sized peptides have a particular mechanism of action that is different to that of large peptides. These results provide additional support for a previously proposed four-step mechanism of action. The possible pharmacophoric requirement for these small-sized peptides is discussed. Furthermore, our results indicate that a net +4 charge is the adequate for 9 amino acid long peptides to produce antibacterial activity. The information reported here is very important for designing new antibacterial peptides with these structural characteristics.

Coccidioidomycosis mimicking testicular cancer: A case report.

We present the case of a 48 year-old man with a history of pulmonary tuberculosis who was brought to our centre with a progressively increasing left testicular mass. Radiological findings were not conclusive on whether the mass was neoplastic or infectious in nature. Therefore, an orchiectomy was performed. Pathology examination revealed coccidioidomycosis of the left testicle, highlighting an exceedingly rare presentation of disseminated genitourinary coccidioidomycosis.