ESR Essentials: using the right scoring system in prostate MRI-practice recommendations by ESUR.

MRI has gained prominence in the diagnostic workup of prostate cancer (PCa) patients, with the Prostate Imaging Reporting and Data System (PI-RADS) being widely used for cancer detection. Beyond PI-RADS, other MRI-based scoring tools have emerged to address broader aspects within the PCa domain. However, the multitude of available MRI-based grading systems has led to inconsistencies in their application within clinical workflows. The Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) assesses the likelihood of clinically significant radiological changes of PCa during active surveillance, and the Prostate Imaging for Local Recurrence Reporting (PI-RR) scoring system evaluates the risk of local recurrence after whole-gland therapies with curative intent. Underlying any system is the requirement to assess image quality using the Prostate Imaging Quality Scoring System (PI-QUAL). This article offers practicing radiologists a comprehensive overview of currently available scoring systems with clinical evidence supporting their use for managing PCa patients to enhance consistency in interpretation and facilitate effective communication with referring clinicians. KEY POINTS: Assessing image quality is essential for all prostate MRI interpretations and the PI-QUAL score represents  the standardized tool for this purpose. Current urological clinical guidelines for prostate cancer diagnosis and localization recommend adhering to the PI-RADS recommendations. The PRECISE and PI-RR scoring systems can be used for assessing radiological changes of prostate cancer during active surveillance and the likelihood of local recurrence after radical treatments respectively.

Discovery of Hit Compounds Targeting the P4 Allosteric Site of K-RAS, Identified through Ensemble-Based Virtual Screening.

Mutants of Ras are oncogenic drivers of a large number of human tumors. Despite being recognized as an attractive target for the treatment of cancer, the high affinity for its substrate tagged the protein as undruggable for a few years. The identification of cryptic pockets on the protein surface gave the opportunity to identify molecules capable of acting as allosteric modulators. Several molecules were disclosed in recent years, with sotorasib and adagrasib already approved for clinical use. The present study makes use of computational methods to characterize eight prospective allosteric pockets (P1-P8) in K-Ras, four of which (P1-P4) were previously characterized in the literature. The present study also describes the results of a virtual screening study focused on the discovery of hit compounds, binders of the P4 site that can be considered as peptidomimetics of a fragment of the SOS αI helix, a guanine exchange factor of Ras. After a detailed description of the computational procedure followed, we disclose five hit compounds, prospective binders of the P4 allosteric site that exhibit an inhibitory capability higher than 30% in a cell proliferation assay at 50 µM.

Effect of Trace Metal Ions on the Conformational Stability of the Visual Photoreceptor Rhodopsin.

Trace metals are essential elements that play key roles in a number of biochemical processes governing human visual physiology in health and disease. Several trace metals, such as zinc, have been shown to play important roles in the visual phototransduction process. In spite of this, there has been little research conducted on the direct effect of trace metal elements on the visual photoreceptor rhodopsin. In the current study, we have determined the effect of several metal ions, such as iron, copper, chromium, manganese, and nickel, on the conformational stability of rhodopsin. To this aim, we analyzed, by means of UV-visible and fluorescence spectroscopic methods, the effects of these trace elements on the thermal stability of dark rhodopsin, the stability of its active Metarhodopsin II conformation, and its chromophore regeneration. Our results show that copper prevented rhodopsin regeneration and slowed down the retinal release process after illumination. In turn, Fe3+, but not Fe2+, increased the thermal stability of the dark inactive conformation of rhodopsin, whereas copper ions markedly decreased it. These findings stress the important role of trace metals in retinal physiology at the photoreceptor level and may be useful for the development of novel therapeutic strategies to treat retinal disease.

Effects of solvents on the conformational profile of Balaram's peptide: a computational study.

The present work reports the results of a computational study aimed at characterizing the conformational profile of Balaram's peptide (Ace-Leu-Val-Val-Aib-Gly-Leu-Val-Val-NHMe) in different solvents, including chloroform, dimethyl sulfoxide, methanol and water. For this purpose, 10 µs molecular dynamics trajectories were computed in explicit solvents for each system, starting from an extended conformation. The results of the present study confirm the former NMR and CD findings and provide further insights that permit fine-tuning of the conclusions previously derived. The present results show that the peptide exhibits a helical conformation in chloroform, but a mixture of ß-hairpin and Ω-shape conformations, as the predominant structures in DMSO and MeOH. Finally, the peptide does not exhibit a preferred conformation in water, although significant populations of helical and ß-hairpin conformations are available. The present results underline the role of solvents in the conformational profile of a peptide and it is an example of the complementarity between computational methods and spectroscopy studies.

Treatment of Bolivian Leishmania braziliensis Cutaneous and Mucosal Leishmaniasis.

Although infection with Leishmania braziliensis is perhaps the key reason to treat New World cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML), the total literature contains relatively few reported cases. With the aim of supplementing the meager clinical information available, we searched the records of Jorochito (Dermatology) Hospital, Bolivia, for the years 1999-2020 and identified treatment records for 1,696 naive CL patients and 355 naive ML patients. Because follow-up was poor for this real-world treatment experience in the developing world, only 255 CL patients (15%) and 114 ML patients (32%) attended follow-up at Hospital. We therefore engaged in an Active Search for "lost" patients, located a further 542 CL patients (32%) and 142 ML patients (44%), thus eventually accomplished follow up on 697 CL patients (41%) and 256 ML patients (72%). Granular adverse event data derived from hospital records is listed for the 902 CL and 86 ML patients administered Glucantime intramuscularly, the 401 CL and 202 ML patients administered Glucantime intravenously, and the 163 CL and 89 ML patients administered miltefosine orally. Efficacy was obtained from hospital records for patients seen at hospital and from patient recall communicated by telephone for the patients found in the Active Search. The overall CL cure rate was 508 of 697 CL patients (73%) with follow-up: intramuscular Glucantime-196/293 (67%); intravenous Glucantime-90/126 (71%); intralesional Glucantime-34/54 (63%); oral miltefosine-52/69 (75%). The overall ML cure rate was 161 of 256 ML patients (63%) with follow-up: intramuscular Glucantime-26/48 (54%); intravenous Glucantime-66/104 (63%); intravenous amphotericin B deoxycholate-19/35 (54%); oral miltefosine-50/71 (70%). We offer this extensive adverse event and efficacy experience as useful guides for clinicians presented with a L. braziliensis infection. The cure rates also illustrate the quandary of New World CL and ML chemotherapy: sufficiently high to be useful but nevertheless needing augmentation with new agents.

Precisión y utilidad de la resonancia magnética para el diagnóstico de cáncer de testículo / Magnetic resonance imaging accuracy and utility for testicular cancer diagnosis

Objetivo: El objetivo de este trabajo es analizar los hallazgos en resonancia magnética testicular (RMt) y el tipo histopatológico de las lesiones para determinar qué características relacionadas con las imágenes pueden constituir predictores de malignidad.Materiales y métodos: Se analizaron de manera retrospectiva 46 pacientes con lesiones testiculares, a quienes se evaluó inicialmente con ultrasonido (US) y luego con RMt empleando un equipo de 1,5 teslas. Los estudios de resonancia magnética (RM) fueron analizados por un radiólogo con 8 años de experiencia en RMt. Los hallazgos en las imágenes como el tamaño de la lesión, la intensidad de señal en secuencias T1, T2, y el realce tras la administración de contraste se correlacionaron con el diagnóstico de anatomía patológica (AP). Se estudió la sensibilidad, la especificidad, el valor predictivo positivo (VPP) y el valor predictivo negativo (VPN).Resultados: El realce tras administración de contraste fue el hallazgo de mejor performance con una sensibilidad, especificidad, VPP y VPN de 90 (71-97), 47 (24-71), 74 (56-87) y 73 (40-92), respectivamente. Los resultados para las lesiones hiperintensas, hipointensas o heterogéneas en secuencias ponderadas en T2 y con realce con el contraste endovenoso fueron de 87 (49-84), 47 (44-89), 74 (55-86) y 67 (35-89), respectivamente (sensibilidad, especificidad, VPP y VPN).Conclusión: El hallazgo de una lesión testicular de baja intensidad de señal y/o heterogénea en secuencias T2, con realce con contraste EV representa un valioso predictor de malignidad. Siendo esta última característica la más sensible como predictor de malignidad en las imágenes. (AU)

Purpose: The purpose of our study is to analyze the imaging findings described in MRI and the histopathologic type of testicular lesions to determine which findings are the best predictors of malignancy.Materials and methods: Forty six (46) patients with testicular lesions were initially studied with ultrasound (US) and with testicular MRI (tMRI) on a 1.5-T magnet. MRIs were reviewed by a radiologist with 8 years of experience and imaging findings such as the size of the lesion, the signal intensity in T1, T2 weighted sequences, and the enhancement after endovenous contrast administration, were correlated with the histopathologic diagnosis. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were analyzed.Results: The enhancement after administration of contrast was the finding of better performance with a sensitivity, specificity, PPV and NPV of 90 (71-97), 47 (24-71), 74 (56-87) and 73 (40-92), respectively. Meanwhile, the results for hypointense/heterogeneous lesions in T2 weighted sequences and with enhancement with intravenous contrast were 87 (49-84), 47 (44-89), 74 (55-86) y 67 (35-89), respectively.Conclusion: The finding of a testicular lesion of low signal intensity and heterogeneous in T2 weighted sequences, with IV contrast enhancement represents a valuable predictor of malignancy. The latter being the most sensitive as a predictor of malignancy. (AU)

Associations between household air pollution and early child development among children aged 36-59 months in Bangladesh.

BACKGROUND: Household air pollution (HAP) from solid fuel use (SFU) for cooking may impact child health in low-resources countries. This study examined the associations between HAP and early childhood development (ECD) outcomes among children under 5 years of age in Bangladesh and explored potential effect modification by sex and urbanicity. METHODS: The study sample consisted of 9395 children aged 36-59 months in the households from the Bangladesh Multiple Indicator Cluster Survey 2019. SFU and levels of exposure to SFU (unexposed, moderately exposed and highly exposed) were used as proxies of HAP exposure. We estimated the covariate-adjusted prevalence ratios (aPRs) and 95% CIs for the associations between HAP and ECD outcomes using multilevel mixed-effects Poisson regression models with a robust variance estimator. RESULTS: 81.4% of children were exposed to SFU, and the prevalence of developmental delay (in Early Childhood Development Index) was 25.3%. Children exposed to SFU were 1.47 times more likely to have developmental delays (95% CI: 1.25, 1.73; p<0.001) compared with children with no SFU exposure. SFU was significantly associated with developmental delay in socioemotional (aPR: 1.17; 95% CI: 1.01, 1.36; p=0.035) and learning-cognitive (aPR: 1.90; 95% CI: 1.39, 2.60; p<0.001) domains. Similarly, children moderately exposed and highly exposed to HAP had higher prevalence of developmental delays than unexposed children. We did not observe effect modification by sex or urbanicity. CONCLUSION: Public health policies should promote the use of clean cooking fuels and cookstoves to reduce the high burden of HAP exposure in low-resource countries for helping younger children to meet their developmental milestones.

[Magnetic resonance imaging accuracy and utility for testicular cancer diagnosis]. / Precisión y utilidad de la resonancia magnética para el diagnóstico de cáncer de testículo.

PURPOSE: The purpose of our study is to analyze the imaging findings described in MRI and the histopathologic type of testicular lesions to determine which findings are the best predictors of malignancy. MATERIALS AND METHODS: Forty six (46) patients with testicular lesions were initially studied with ultrasound (US) and with testicular MRI (tMRI) on a 1.5-T magnet. MRIs were reviewed by a radiologist with 8 years of experience and imaging findings such as the size of the lesion, the signal intensity in T1, T2 weighted sequences, and the enhancement after endovenous contrast administration, were correlated with the histopathologic diagnosis. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were analyzed. RESULTS: The enhancement after administration of contrast was the finding of better performance with a sensitivity, specificity, PPV and NPV of 90 (71-97), 47 (24-71), 74 (56-87) and 73 (40-92), respectively. Meanwhile, the results for hypointense/heterogeneous lesions in T2 weighted sequences and with enhancement with intravenous contrast were 87 (49-84), 47 (44-89), 74 (55-86) y 67 (35-89), respectively. CONCLUSION: The finding of a testicular lesion of low signal intensity and heterogeneous in T2 weighted sequences, with IV contrast enhancement represents a valuable predictor of malignancy. The latter being the most sensitive as a predictor of malignancy.

Venous Thromboembolism in Patients with Cancer Receiving Specialist Palliative Care.

CONTEXT: The prevalence of venous thromboembolism (VTE) in patients with cancer is particularly high at disease progression and during relapse. Patients cared for in specialized palliative care units (SPCU) are rarely included in VTE studies. Objective: We sought to study the prevalence, clinical characteristics, and survival of individuals with VTE in an SPCU setting. METHODS: We retrospectively included 2707 consecutive individuals with active cancer managed at a SPCU. Data were summarized using descriptive statistics and frequency for categorical variables. Overall survival was estimated by Kaplan-Meier and comparisons by log-rank test. Thrombotic events were confirmed by imaging. RESULTS: We studied 1984(73.3%) women and 723 (26.7%) men. The overall prevalence of thrombosis was 22.2% with only 6.2% occurring after initiating SPCU care, and was higher in women (24.6% vs 15.8%), particularly with gynecological tumors (cervical: 30.5%, ovarian: 29.2%). Median survival was slightly longer for patients without VTE (80 days [IQR21-334] and 69 days [IQR 25-235]; p = 0.03). CONCLUSIONS: Prevalence of VTE was high and varied by tumor origin. VTE may impact survival. Though median survival is short, some patients are followed over months, suggesting that in the absence of high bleeding risk, treatment for thrombosis in an attempt to decrease the morbidity of re-thrombosis should be considered. On the other hand, few patients developed symptomatic VTE during SPCU care, making generalized primary prophylaxis probably unwarranted. Customizing anticoagulation for the risk of hemorrhage and physical performance is essential.

Structure-Activity Studies of Novel Di-substituted [1,2,5]oxadiazolo [3,4-b]pyrazine Analogs Targeting the A-loop Regulatory Site of p38 MAP Kinase.

INTRODUCTION: In the quest for novel allosteric inhibitors of the p38 MAP kinase, we recently described the A-loop regulatory site, identified by means of molecular modeling studies together with the disclosure of a small molecule hit with a moderate inhibitory profile. Starting from this structure, we subsequently identified two additional hits with simpler molecular structures from an in silico screening study, using a substructure search in the SciFinder database. After corroboration of their inhibitory profile, analysis of their structures permitted to conclude about the suitability of the [1,2,5]oxadiazolo[3,4-b]pyrazine (furazano[ 3,4-b]pyrazine) scaffold for the development of potent A-loop regulatory site p38 MAP kinase inhibitors. Accordingly, we report the synthesis and pharmacological evaluation of a series of di-substituted analogs with a potent inhibitory profile of p38 MAP kinase, as shown by in vitro assays of their capability to inhibit IL-1ß secretion in human monocyte-derived macrophages. OBJECTIVE: To find small molecule potent inhibitors of the p38 MAP kinase A-loop regulatory site. METHODS: Starting from this structure, we subsequently identified two additional hits with simpler molecular structures from an in silico screening study, using a substructure search in the SciFinder database. After corroboration of their inhibitory profile, we carried out a hit-tolead optimization process guided by molecular modeling using a [1,2,5]oxadiazolo[3,4- b]pyrazine (furazano[3,4-b]pyrazine) scaffold. RESULTS: We report the synthesis and pharmacological evaluation of a series of di-substituted analogs with a potent inhibitory profile of p38 MAP kinase, as shown by in vitro assays of their capability to inhibit IL-1ß secretion in human monocyte-derived macrophages. CONCLUSION: We describe in the present work a series of [1,2,5]oxadiazolo[3,4-b]pyrazine (furazano[3,4-b]pyrazine), which are potent inhibitors of IL-1ß secretion in human monocytederived macrophages allosteric modulators of the p38 MAP kinase A-loop regulatory site.

Discovery of Diverse Natural Products as Inhibitors of SARS-CoV-2 Mpro Protease through Virtual Screening.

SARS-CoV-2 is a type of coronavirus responsible for the international outbreak of respiratory illness termed COVID-19 that forced the World Health Organization to declare a pandemic infectious disease situation of international concern at the beginning of 2020. The need for a swift response against COVID-19 prompted to consider different sources to identify bioactive compounds that can be used as therapeutic agents, including available drugs and natural products. Accordingly, this work reports the results of a virtual screening process aimed at identifying antiviral natural product inhibitors of the SARS-CoV-2 Mpro viral protease. For this purpose, ca. 2000 compounds of the Selleck database of Natural Compounds were the subject of an ensemble docking process targeting the Mpro protease. Molecules that showed binding to most of the protein conformations were retained for a further step that involved the computation of the binding free energy of the ligand-Mpro complex along a molecular dynamics trajectory. The compounds that showed a smooth binding free energy behavior were selected for in vitro testing. From the resulting set of compounds, five compounds exhibited an antiviral profile, and they are disclosed in the present work.

Case Report: Mini-endoscopic combined intrarenal surgery in an en-bloc kidney transplant.

BACKGROUND: Overall incidence of stones in kidney transplant recipients is 1%. En-bloc kidney transplant is a rare anatomical condition in which kidney stones treatment can be extremely difficult to treat. As far as we know, no cases of staghorn calculi in en-bloc kidney transplant have been published so far. CASE PRESENTATION: A 27-year-old woman presented to the Emergency Department because of asthenia, adynamia and weight loss associated with lower urinary tract symptoms and subfebrile temperature. Ten years before, she had undergone an en-bloc kidney transplant because of end-stage renal disease secondary to perinatal asphyxia syndrome. One kidney was implanted capo-volta in the right iliac fossa and the other one in the right flank. NCCT scan showed incomplete staghorn calculi in the iliac fossa transplanted kidney. Besides, severe dilation of the native and the right flank transplanted kidney, due to two ureteral stones of 6 and 7 mm impacted in the uretero-ureteral anastomosis, was found. After hospital admission and under ceftriaxone prophylaxis, an attempt to perform primary RIRS following our COVID protocol was carried out. Nevertheless, we ended up placing a JJ stent because once the guidewire passed through the ureteral stones, purulent material came out from the ureteral orifice. She stayed 9 days in-hospital for management of postobstructive polyuria and was discharged with oral antibiotics. Three weeks afterward, we removed the stent and performed flexible ureteroscopy and holmium laser lithotripsy of the ureteral stones. In the same procedure, we performed Mini-ECIRS (21 French) previous ultrasound-guided upper pole puncture. Postoperative NCCT scan showed neither residual fragments nor operative complications. CONCLUSION: This is the first clinical case reporting Mini-ECIRS in a patient with an en-bloc kidney transplant. This endourological approach seems to be a feasible, safe and effective approach to treat stones in this anatomically challenging condition.

Discovery of novel 2,3,5-trisubstituted pyridine analogs as potent inhibitors of IL-1ß via modulation of the p38 MAPK signaling pathway.

Interleukin-1ß is a central mediator of innate immune responses and inflammation. It plays a key role in a wide variety of pathologies, ranging from autoinflammatory diseases to metabolic syndrome and malignant tumors. It is well established that its inhibition results in a rapid and sustained reduction in disease severity, underlining the importance of having a repertoire of drugs of this class. At present, there are only three interleukin-1ß blockers approved in the clinic. All of them are biologics, requiring parenteral administration and resulting in expensive treatments. In an exercise to identify small molecule allosteric inhibitors of MAP kinases, we discovered a series of compounds that block IL-1ß release produced as a consequence of a stimulus involved in triggering an inflammatory response. The present study reports the hit-to-lead optimization process that permitted the identification of the compound 13b (AIK3-305) an orally available, potent and selective inhibitor of IL-1ß. Furthermore, the study also reports the results of an in vivo efficacy study of 13b in a LPS endotoxic shock model in male BALB/c mice, where IL-1ß inhibition is monitored in different tissues.

Effect of exercise on symptoms of premenstrual syndrome in low and middle-income countries: a protocol for systematic review and meta-analysis.

INTRODUCTION: Premenstrual syndrome (PMS) has the potential to affect the quality of life adversely. Published guidelines recommend the use of exercise as part of the first-line management interventions for PMS. However, the published evidence related to the effectiveness of physical activity and PMS is inconclusive. This review will assess the effectiveness of exercise-based interventions in reducing PMS in women screened or diagnosed with PMS in low and middle-income countries, where the prevalence of PMS is high. METHODS AND ANALYSIS: Electronic databases will be researched, including Embase, Cochrane Central Register of Controlled Trials, MEDLINE, PsycINFO, Web of Science, ClinicalTrials.gov and Google Scholar. All the studies published until March 2020 will be included. A standardised data extraction form will be used adapted from the Cochrane Handbook of Systematic Reviews of Interventions. Included articles will be assessed using the risk of bias tools based on study design. Data will be analysed using Review Manager V.5.3. The inverse-variance random-effects method will be used to report the standardised mean difference. A meta-analysis will be used only if studies are sufficiently homogenous. A narrative synthesis will be undertaken when studies are heterogeneous. Methodological heterogeneity between studies will be evaluated by considering the study types. Statistical heterogeneity will be tested using the I2 test. Subgroup analyses may be performed only for the primary outcome in case of sufficient studies. Sensitivity analysis will be conducted to assess the impact of intervention excluding studies without randomisation and studies with a high risk of bias. Funnel plots will be used to assess the potential reporting bias and small-study effects only when there are more than 10 studies included in the meta-analysis. ETHICS AND DISSEMINATION: This study does not require ethical approval, as the review is entirely based on published studies. The results will be published and/or will be presented at a pertinent conference. PROSPERO REGISTRATION NUMBER: CRD42020163377.

Molecular Features of Non-Selective Small Molecule Antagonists of the Bradykinin Receptors.

Angiotensin converting enzyme 2 (ACE2) downregulation is a key negative factor for the severity of lung edema and acute lung failure observed in patients infected with SARS-CoV-2. ACE2 downregulation affects the levels of diverse peptide mediators of the renin-agiotensin-aldestosterone and kallikrein-kinin systems, compromising vascular hemostasis. Increasing evidence suggests that the inflammatory response observed in covid-19 patients is initiated by the action of kinins on the bradykinin receptors. Accordingly, the use of bradykinin antagonists should be considered as a strategy for therapeutic intervention against covid-19 illness progression. Presently, icatibant is the only bradykinin antagonist drug approved. In the present report, we investigated the molecular features characterizing non-selective antagonists targeting the bradykinin receptors and carried out a in silico screening of approved drugs, aimed at the identification of compounds with a non-selective bradykinin antagonist profile that can be evaluated for drug repurposing. The study permitted to identify eight compounds as prospective non-selective antagonists of the bradykinin receptors, including raloxifene; sildenafil; cefepime; cefpirome; imatinib; ponatinib; abemaciclib and entrectinib.

Importance of structure-based studies for the design of a novel HIV-1 inhibitor peptide.

Based on the structure of an HIV-1 entry inhibitor peptide two stapled- and a retro-enantio peptides have been designed to provide novel prevention interventions against HIV transmission. The three peptides show greater inhibitory potencies in cellular and mucosal tissue pre-clinical models than the parent sequence and the retro-enantio shows a strengthened proteolytic stability. Since HIV-1 fusion inhibitor peptides need to be embedded in the membrane to properly interact with their viral target, the structural features were determined by NMR spectroscopy in micelles and solved by using restrained molecular dynamics calculations. Both parent and retro-enantio peptides demonstrate a topology compatible with a shared helix-turn-helix conformation and assemble similarly in the membrane maintaining the active conformation needed for its interaction with the viral target site. This study represents a straightforward approach to design new targeted peptides as HIV-1 fusion inhibitors and lead us to define a retro-enantio peptide as a good candidate for pre-exposure prophylaxis against HIV-1.

New Insights into the Stereochemical Requirements of the Bombesin BB1 Receptor Antagonists Binding.

Members of the family of bombesinlike peptides exert a wide range of biological activities both at the central nervous system and in peripheral tissues through at least three G-Protein Coupled Receptors: BB1, BB2 and BB3. Despite the number of peptide ligands already described, only a few small molecule binders have been disclosed so far, hampering a deeper understanding of their pharmacology. In order to have a deeper understanding of the stereochemical features characterizing binding to the BB1 receptor, we performed the molecular modeling study consisting of the construction of a 3D model of the receptor by homology modeling followed by a docking study of the peptoids PD168368 and PD176252 onto it. Analysis of the complexes permitted us to propose prospective bound conformations of the compounds, consistent with the experimental information available. Subsequently, we defined a pharmacophore describing minimal stereochemical requirements for binding to the BB1 receptor that was used in silico screening. This exercise yielded a set of small molecules that were purchased and tested, showing affinity to the BB1 but not to the BB2 receptor. These molecules exhibit scaffolds of diverse chemical families that can be used as a starting point for the development of novel BB1 antagonists.

[Mucinous cystadenoma of the ileocecal valve. Uncommon intestinal tumor in a oneyear-old boy. Case report]. / Cistoadenoma mucinoso de la vá lvula ileocecal: tumoración intestinal infrecuente en un niñ o de 1 añ o. Reporte de caso.

Mucinous cystadenoma is usually found in the ovary, pancreas and appendix but its presentation in the intestine is extremely rare. In this case report we present an infant with partial intestinal occlusion due to a mucinous cystadenoma of the ileocecal valve. We performed an excision of the terminal ileum, ileocecal valve, cecum and appendix, followed by ileocolic anastomosis. The patient did well after the procedure and recovered uneventfully. To our knowledge, this is the first case report of this tumor in this location.

Assessment of the conformational profile of bombesin by computational methods.

In the present work, the results of a computational study aimed at assessing the conformational profile of bombesin are reported. The conformational space of the peptide was sampled by means of a 4 µs accelerated molecular dynamics simulation in water, using an explicit solvent model. The results were analyzed using Principal Component Analysis to get essential information on peptide fluctuations, along with cluster analysis to characterize different conformations in the sample. Analysis of the results suggests that the peptide adopts helical structures at the C-terminus that tend to unwind at the end of the peptide chain, since there are many structures exhibiting only two turns of a helix at the central segment of the peptide. In addition, the peptide also adopts hairpin turn structures at the N-terminus. Results of the simulation were confronted with available NMR results in a 2,2,2-trifluoroethanol/water (30% v/v) solution. Distances deduced form NOEs experiments only provide support to the presence of helical conformations that represent the most populated structures in the simulation. The absence of other conformations in the NMR experiments can be explained to be due to the α-helix enhancing nature of the solvent used in the experiments.