The effects of simultaneous respiratory infections on the nasal shedding of Mycoplasmopsis bovirhinis in dairy calves.

Although there are several studies that described the possible participation of Mycoplasmopsis bovirhinis (formerly, Mycoplasma bovirhinis) in respiratory disease in calves worldwide, none of these evaluated the effects of concomitant infections on the shedding of this organism. Accordingly, this study evaluated the effects of simultaneous respiratory infections in dairy calves on the nasal shedding of M. bovirhinis. A statistical two-step model, using univariable and multivariable with logistic regression was developed to investigate and predict the possible effects of simultaneous infections by Histophilus somni, Mannheimia haemolytica, Pasteurella multocida, bovine coronavirus (BCoV), and ovine gammaherpesvirus 2 (OvGHV2) in dairy calves on the nasal shedding of M. bovirhinis. The multivariable analysis demonstrated that dairy calves infected with OvGHV2 have 2.59 times likelihood of nasal shedding of M. bovirhinis relative to calves not infected by OvGHV2, while the odds of nasal shedding of M. bovirhinis was 3.46 times higher in dairy calves infected by M. haemolytica. In contrast, simultaneous respiratory infections in dairy calves by H. somni, P. multocida, and BCoV had no direct effect on the nasal shedding of M. bovirhinis. Consequently, infections by OvGHV2 and M. haemolytica may be possible risk factors for the nasal shedding of M. bovirhinis in dairy calves. These results demonstrated the importance of disease modeling in veterinary medicine to predict and understand the complex outcomes of associations in animals concomitantly infected by several disease pathogens.

Relationship between obesity severity and Helicobacter pylori eradication in patients undergoing bariatric and metabolic surgery: A post hoc analysis.

BACKGROUND: The global prevalence of obesity is increasing and represents a major public health challenge. However, there is a paucity of data regarding Helicobacter pylori (H pylori) eradication in people with obesity. The aim of the study is to examine the influence of obesity degree on H. pylori eradication in patients undergoing bariatric and metabolic surgery. METHODS: A post hoc analysis was conducted in a cohort of 204 adults patients (129 individuals diagnosed with obesity, 75 normal weight) H. pylori positive, included in two multicenter, prospective studies. Patients underwent a 14-day quadruple concomitant treatment, and H. pylori eradication was assessed using the 13C-urea breath test. The cohort was stratified according to body mass index (BMI), and statistical analyses were performed using chi-squared test, Kruskal-Wallis test, and logistic regression. RESULTS: Eradication rates were significantly lower in patients with obesity compared with normal weight individuals (68.2% vs. 88.0%, OR 0.29, 95% CI 0.13-0.63, p < 0.01). Furthermore, within the population diagnosed with obesity, the degree of obesity correlated with decreased eradication rates, with class 3 (BMI 40.0-49.9) and class 4 (BMI ≥ 50.0) obesity showing the lowest rates (67% and 51%, with an OR 0.28 and 0.15 respectively, p < 0.01). CONCLUSIONS: Our results indicate that obesity may influence H. pylori eradication, especially among severe obesity patients undergoing bariatric surgery, which could have implications for the development of ulcers and gastritis as well as the risk of gastric cancer. Tailored eradication strategies may be necessary to improve treatment efficacy in this population.

Real-world utilization pattern of dydrogesterone in 7287 Indian women with obstetric and gynecological conditions: data from multicentric, retrospective study.

Objective: Despite the literature on dydrogesterone, studies on dydrogesterone utilization patterns are largely lacking in Indian patients. Methods: This was a multi-center, retrospective, observational, cross-sectional, and descriptive study across 817 centers in India. Data of patients who received dydrogesterone in past and provided consent for future use of their medical record for research purpose was were retrieved and analyzed. Results: Data of 7287 subjects (aged 29.55±4.84 years) was analyzed. Threatened abortion was the most common indication for which the subjects received dydrogesterone (46.9%) followed by recurrent pregnancy loss. Polycystic ovary syndrome (PCOS), thyroid disorders and anemia were the most common comorbid conditions and prior pregnancy loss, advanced maternal age and obesity were the most common risk factors seen in subjects who received dydrogesterone. Total 27.5% of subjects received a loading dose of dydrogesterone, and majority (64%) received 40 mg as loading dose. 10 mg dose was used as maintenance or regular dose in 81.4% of the subjects. Twice daily (BID) was the most common dosing frequency (66.6%). The most common concomitant medications being taken by the subjects on dydrogesterone included folic acid (45.1%), iron supplements (30.3%) and calcium and vitamin D3 supplements (25.5%). Another progesterone preparation (oral, injection, vaginal, tubal) other than dydrogesterone was used concurrently in 7.8% of subjects. Conclusion: The study helped to identify the patient population that is benefitted by dydrogesterone and the preferred indications, risk factors, comorbid conditions and concomitant medication used in this patient population at real-life scenario.

Surgical treatment of pituitary neuroendocrine tumors with coexisting intracranial lesions: A case series and review of the literature.

Background: Pituitary neuroendocrine tumors (PitNETs) are a diverse group of benign neoplasms that account for a significant proportion of intracranial tumors (13%). The coexistence of PitNET with other intracranial lesions, such as meningiomas and intracranial aneurysms, has been constantly reported in the literature; yet, the pathophysiological mechanisms remain unknown, and the appropriate management is controversial. This study aims to describe the clinical characteristics, surgical treatment, and outcomes of patients with PitNET with coexisting intracranial lesions in a single healthcare center. Methods: A retrospective analysis was conducted on 12 patients who underwent surgical treatment for PitNET and another intracranial lesion at our single tertiary referral center over 15 years from January 2008 to May 2023. Results: Among these coexisting lesions, aneurysms were the most commonly found (41.67%), followed by meningiomas (33.33%). Surgical intervention for both lesions was performed in a single-stage procedure for most cases (75%), employing transcranial, endoscopic endonasal, and combined approaches. We found low preoperative Karnofsky Performance Scale scores in three patients, with significant differences in functional outcomes. Conclusion: These findings contribute to the limited knowledge about PitNET coexisting with other intracranial lesions and emphasize the importance of patient-tailored, multidisciplinary management in these unusual scenarios.

Prediction Models for Adverse Drug Reactions During Tuberculosis Treatment in Brazil.

BACKGROUND: Tuberculosis (TB) treatment-related adverse drug reactions (TB-ADRs) can negatively affect adherence and treatment success rates. METHODS: We developed prediction models for TB-ADRs, considering participants with drug-susceptible pulmonary TB who initiated standard TB therapy. TB-ADRs were determined by the physician attending the participant, assessing causality to TB drugs, the affected organ system, and grade. Potential baseline predictors of TB-ADR included concomitant medication (CM) use, human immunodeficiency virus (HIV) status, glycated hemoglobin (HbA1c), age, body mass index (BMI), sex, substance use, and TB drug metabolism variables (NAT2 acetylator profiles). The models were developed through bootstrapped backward selection. Cox regression was used to evaluate TB-ADR risk. RESULTS: There were 156 TB-ADRs among 102 of the 945 (11%) participants included. Most TB-ADRs were hepatic (n = 82 [53%]), of moderate severity (grade 2; n = 121 [78%]), and occurred in NAT2 slow acetylators (n = 62 [61%]). The main prediction model included CM use, HbA1c, alcohol use, HIV seropositivity, BMI, and age, with robust performance (c-statistic = 0.79 [95% confidence interval {CI}, .74-.83) and fit (optimism-corrected slope and intercept of -0.09 and 0.94, respectively). An alternative model replacing BMI with NAT2 had similar performance. HIV seropositivity (hazard ratio [HR], 2.68 [95% CI, 1.75-4.09]) and CM use (HR, 5.26 [95% CI, 2.63-10.52]) increased TB-ADR risk. CONCLUSIONS: The models, with clinical variables and with NAT2, were highly predictive of TB-ADRs.

Eco-epidemiological study of seropositivity against Rickettsia and Leptospira agents in rural areas of Urabá, Colombia.

Rickettsioses and leptospirosis are infectious diseases that are often underdiagnosed due to a lack of knowledge about their epidemiology, pathophysiology, diagnosis, management, among others. Objetive: to characterize the seroprevalence and seroincidence of both Rickettsia and Leptospira agents and determine the risk factors for these outcomes in rural areas of Urabá, Antioquia. Methods: a secondary data analysis using information on Rickettsia and Leptospira exposure from a prior prospective study that explored sociocultural and ecological aspects of Rickettsia infection in rural Urabá, Colombia. A multinomial mixed logistic regression model was employed to analyze factors linked to seroprevalent cases of Rickettsia, Leptospira and both, along with descriptive analyses of seroincident cases. Results: the concomitant seroprevalence against Rickettsiaand Leptospira was 9.38% [95%CI 6.08%-13.37%] (56/597). The factors associated with this seroprevalence were age (ORa= 1.02 [95%CI 1.007-1.03]), male gender (ORa= 3.06 [95%CI 1.75-5.37]), fever history (ORa= 1.71 [95%CI 1.06-2.77]) the presence of breeding pigs (ORa= 2.29 [95%CI 1.36-3.88]), peridomicile yucca crops(ORa= 2.5 [95%CI 1.1-5.62]), and deforestation practices(ORa= 1.74 [95%CI 1.06-2.87]). The concomitant seroincidence against Rickettsia and Leptospira was 1.09% (3/274) [95%CI 0.29%-4.05%], three cases were female, with a median age of 31.83 years-old (IQR 8.69-56.99). At the household level, all the seroincident cases had households built partially or totally with soil floors, wooden walls, and zinc roofs. Two seroincident cases described the presence of equines, canines, and domestic chickens in intra or peri-domicile. Finally, two cases were exposed to synanthropic rodents, and one case to tick infestation. Conclusion: there is evidence of seroprevalent and seroincident cases of seropositivity against both Rickettsia and Leptospira in rural areas of Urabá, Colombia. These findings can help improve public health surveillance systems in preventing, detecting, and attending to the different clinical cases caused by these pathogens.

Real-world utilization pattern of dydrogesterone in 7287 Indian women with obstetric and gynecological conditions: data from multicentric, retrospective study

Abstract Objective: Despite the literature on dydrogesterone, studies on dydrogesterone utilization patterns are largely lacking in Indian patients. Methods: This was a multi-center, retrospective, observational, cross-sectional, and descriptive study across 817 centers in India. Data of patients who received dydrogesterone in past and provided consent for future use of their medical record for research purpose was were retrieved and analyzed. Results: Data of 7287 subjects (aged 29.55±4.84 years) was analyzed. Threatened abortion was the most common indication for which the subjects received dydrogesterone (46.9%) followed by recurrent pregnancy loss. Polycystic ovary syndrome (PCOS), thyroid disorders and anemia were the most common comorbid conditions and prior pregnancy loss, advanced maternal age and obesity were the most common risk factors seen in subjects who received dydrogesterone. Total 27.5% of subjects received a loading dose of dydrogesterone, and majority (64%) received 40 mg as loading dose. 10 mg dose was used as maintenance or regular dose in 81.4% of the subjects. Twice daily (BID) was the most common dosing frequency (66.6%). The most common concomitant medications being taken by the subjects on dydrogesterone included folic acid (45.1%), iron supplements (30.3%) and calcium and vitamin D3 supplements (25.5%). Another progesterone preparation (oral, injection, vaginal, tubal) other than dydrogesterone was used concurrently in 7.8% of subjects. Conclusion: The study helped to identify the patient population that is benefitted by dydrogesterone and the preferred indications, risk factors, comorbid conditions and concomitant medication used in this patient population at real-life scenario.

A rare case of a right infratentorial meningioma and a left giant posterior communicating thrombosed aneurysm.

Background: Giant intracranial aneurysms cause symptoms due to mass effect and can mimic other lesions in imaging studies. The coexistence of tumors and aneurysms is relatively rare, with meningiomas being the predominant tumors found in such cases. The relationship between these two entities is complex and represent a neurosurgical challenge. Case Description: A 61-year-old woman presented with intermittent headache, vertigo, right peripheral facial palsy, hearing loss, and left hemiparesis. Magnetic resonance imaging revealed two lesions: a supratentorial paraclinoid lesion in the left frontotemporal region and a right infratentorial extra-axial mass, suggestive of a meningioma. The patient underwent a two-staged surgical intervention to address both lesions. Conclusion: In this particular case, the lesions were located on different sides and in different cranial compartments, making it even rarer.

The negative effect of concomitant medications on immunotherapy in non-small cell lung cancer: An umbrella review.

BACKGROUND: Conflicting results about the effect of concomitant medications on immunotherapy in non-small cell lung cancer (NSCLC) were reported by many meta-analyses (MAs), and the certainty of evidence linking concomitant medications with immunotherapy efficacy has not been quantified, which may cause some evidence to be misinterpreted. METHODS: Four databases including Embase, Cochrane Library, PubMed, and Web of Science were searched from inception to January 2023 in English. Based on prospective or retrospective clinical controlled trials including immunotherapy with concomitant medications or not in NSCLC, quantitative MAs reporting the efficacy of immunotherapy with binary direct comparison and enough extractable data were collected. The methodological quality, reporting quality, and risk of bias of included MAs were evaluated respectively. New meta-analyses were conducted and their evidence certainty was classified as nonsignificant, weak, suggestive, highly suggestive, or convincing. RESULTS: Fifteen MAs with 5 medications were included. After being assessed by AMSTAR-2, PRISMA, and ROBIS, the major shortcomings were focused on the registration of protocol, literature retrieval or data extraction, implementation of sensitivity analysis or evidence certainty assessment, and incomplete reporting in the section of method and result. New pooled analyses indicated that antibiotics (HR = 1.545[1.318-1.811]), steroids (HR = 1.784[1.520-2.093]), proton pump inhibitors (PPIs) (HR = 1.303[1.048-1.621]) and opioids (HR = 1.910[1.213-3.006]) could shorten overall survival (OS) in patients with NSCLC receiving immunotherapy. Besides, antibiotics (HR = 1.285[1.129-1.462]) and steroids (HR = 1.613[1.315-1.979]) were harmful to progression-free survival (PFS) in these patients significantly. No negative effect was found in nonsteroidal anti-inflammatory drugs and the objective response rate of all medications. High-level evidence suggested that using PPIs before or after the initiation of immunotherapy and using steroids during the first-course immunotherapy could weaken the OS of patients with NSCLC. Meanwhile, the negative effects of antibiotics and opioids on OS or PFS were only supported by moderate or low-level evidence. CONCLUSIONS: The concurrent usage of PPIs or steroids adversely affects the survival of patients with NSCLC receiving immunotherapy. Future investigations are required to ascertain whether these adverse effects are primarily attributed to the comorbidities or the concurrent medications.

Upper gastrointestinal endoscopic findings in celiac disease at diagnosis: A multicenter international retrospective study.

BACKGROUND: Gastroduodenal endoscopy and biopsy following positive specific serology is considered the gold standard to diagnose celiac disease (CeD) in adults. Whether upper endoscopy helps detect comorbid conditions is unknown. AIM: To investigate the prevalence of non-celiac endoscopic findings in patients in whom endoscopy was performed to confirm CeD diagnosis. METHODS: This is an observational, descriptive, multicenter, retrospective study that reports endoscopic findings obtained in adult patients enrolled in local registries from four tertiary centers. We collected data reported on first endoscopy, indicated for investigation of CeD. Diagnosis of CeD was performed by histology (≥ Marsh 2 type mucosal damage) and specific serology. Two European and one North American center included biopsy-confirmed CeD following positive serology. A fourth center (South America) included symptomatic patients undergoing endoscopy, irrespective of CeD serology. The latter cohort included a non-CeD control group. RESULTS: A total of 1328 patients (80% female; 35 years median age) were enrolled, of whom 95.6% had positive specific serology. In 135 patients, endoscopy revealed 163 abnormalities unrelated to CeD (prevalence: 10.1%). Erosive reflux esophagitis (6.4%), gastric erosions (2.0%), and suspicion of esophageal metaplasia (1.2%) were the most common findings. Biopsy-confirmed Barrett's esophagus was infrequent (0.2%). No endoscopic cancer was detected. Older patients (≥ 51 years of age) had a higher prevalence of endoscopic findings than those ≤ 50 (P < 0.01). Within the South American cohort, CeD was associated with a lower rate (8.2%) of comorbid endoscopic findings compared with controls (29.1%; P < 0.001). In the adjusted multivariate analysis of this cohort, having CeD was associated with a 72% reduction in the risk of any endoscopic abnormality (P < 0.0001), and having alarm symptoms was associated with a 37% reduction in the risk of finding at least one endoscopic lesion (P < 0.02). CONCLUSION: In this large multicenter study, young adults with positive CeD serology had few comorbid endoscopic findings. Although patients over 51 years had a high prevalence of non-CeD gastroduodenal mucosal damage, no malignancy or premalignant lesions were found.

Caracterización del Traumatismo Dentoalveolar Concomitante a Trauma Maxilofacial en Personal Profesional de Fuerzas Armadas: Revisión Narrativa

El trauma maxilofacial es un problema de salud pública, comúnmente asociado a traumatismo dentoalveolar. Su prevalencia es alta, siendo más frecuente en poblaciones de riesgo, como personal de Fuerzas Armadas, esto por sus actividades laborales, generando gran impacto en el paciente. Caracterizar, según la literatura, el traumatismo dentoalveolar concomitante a trauma maxilofacial en el personal profesional de Fuerzas Armadas. Se realizó una revisión narrativa en cuatro bases de datos, en octubre del 2020. Se incluyeron publicaciones de máximo 5 años de antigüedad, en inglés o español, con resumen disponible, estudios primarios y revisiones sistemáticas. Se excluyó publicaciones no disponibles en texto completo y reportes de casos. Se incluyeron 15 artículos. Existe un déficit de evidencia sobre la asociación que existe entre traumatismo dentoalveolar y traumatismo maxilofacial en la población estudiada. Encontrándose que solo el 6,7 % de estos incluía en su análisis la concomitancia entre ambos tipos de traumas. Sin embargo, los diagnósticos más prevalentes consistieron en fracturas coronarias y mandibulares, respectivamente, asociadas a actividades de entrenamiento y combate. Se establece que el tipo de trauma maxilofacial más frecuente en la población profesional de Fuerzas Armadas es la fractura mandibular y en relación al traumatismo dentoalveolar, la fractura coronaria. En cuanto a la etiología, destacan las heridas de bala, explosivos y accidentes en vehículos, afectando principalmente a personal del Ejército entre 18 a 30 años. Es importante mencionar que los artículos incluidos en esta revisión que hacen referencia a la concomitancia entre el traumatismo dentoalveolar y maxilofacial son escasos y no se encuentran actualizados, por lo que, se necesita continuar investigando en esta temática.

The maxillofacial injuries are a public health issue commonly associated to dentoalveolar injuries. Its high prevalence in risk population such as the Armed Forces personnel, due to their work activities, generates a great impact on the patient. Characterize, according to the literature, dentoalveolar injuries within the maxillofacial injuries in professional Armed Forces personnel. A narrative research was conducted on October 2020 with four data bases. Only 5-year-old publications were considered both in English and Spanish, including their available summary, primary studies and systematic revisions. Publications without full access or report cases were not included. Fifteen scientific papers were included. There is a deficit of evidence between maxillofacial and dentoalveolar injuries in the target population. Only 6.7 % of the research included a joint analysis between both traumas, however the most prevalent diagnosis consisted in coronaries and mandibular fractures, in that order, associated mainly to training and combat activities. The most frequent maxillofacial injury within the Armed Forces personnel is the mandibular fracture, and in relation with dentoalveolar injuries is the coronary fracture. Regarding the etiology, gunshot wounds, explosives and car accidents are featured affecting mainly between 18 to 30 years old army personnel. It's relevant to highlight that the scientific papers included in this revision about the association between dentoalveolar and maxillofacial injuries are poor and not updated. Further research is needed in this issue.

Caracterización de la hidradenitis supurativa en centro dermatológico colombiano durante el periodo del 2016 al 2019 / Characterization of hidradenitis suppurativa on a Colombian dermatological center, 2016-2019

Resumen Antecedentes: La hidradenitis supurativa (HS) es una enfermedad inflamatoria crónica de la piel. Se relaciona con diferentes factores que podrían incrementar la severidad, pero algunos son poco conocidos o controvertidos. Dado su alto impacto social, deterioro de la calidad de vida y falta de estudios epidemiológicos en Colombia, decidimos describir las variables relacionadas en pacientes con HS atendidos en un centro dermatológico colombiano. Métodos: Se realizó un estudio descriptivo y retrospectivo en un centro dermatológico de Bogotá. Los datos se obtuvieron de los registros médicos de enero de 2016 a diciembre de 2019. Analizamos edad, sexo, índice de masa corporal (IMC), hipertensión, relación premensual, antecedentes familiares de HS, presencia de acné, severidad y ubicación de las lesiones. Resultados: De 24 pacientes, 18 eran mujeres. La mediana de edad fue de 30 años. La mediana del IMC fue de 22,8 Kg / m². El 25% de los casos eran fumadores, el 12,5% tenía hipertensión arterial, el 25% tenía antecedentes familiares de HS, el 20,8% coexistió con acné. Además, el 38,9% de las mujeres informaron un empeoramiento de la sintomatología de la HS en el período premenstrual. La localización más común fue la axila (58,3%). El estadio I de Hurley fue el más frecuente (41,7%). Conclusiones: Este es el primer estudio epidemiológico en Colombia y uno de los pocos publicados en Latinoamérica. Estamos ante una enfermedad crónica con un diagnóstico frecuentemente retrasado, de difícil tratamiento y que afecta la calidad de vida. Es importante hacer una intervención temprana para mejorar el pronóstico. Finalmente se necesitan más estudios sobre las principales características de la HS.

Abstract Background: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease. It is related to different factors that could increase the severity, but some are not well known or are controversial. Given its high social impact and quality of life impairment and the lack of epidemiological studies in Colombia, we described disease variables in patients with HS treated at a colombian dermatological center. Methods: A descriptive and retrospective study was carried out in a dermatological center in Bogota. Data were collected from medical records from January 2016 to December 2019. We analyzed age, sex, boy mass index (BMI), hypertension, pre-monthly relationship, family history of HS, acne presence, severity and lesion locations. Results: Of 24 patients, 18 were women. The median age was 30 years . The BMI median was 22,8 Kg/m². The 25% of cases were smoker, 12,5% had arterial hypertension, 25% had family history of HS, 20.8% had coexistence with acne. Also, 38.9% of women reported worsening symptomatology of HS in the premenstrual period. The most common location was the armpit (58.3%). Hurley stage I was the most frequent (41.7%). Conclusions: This is the first epidemiological study in Colombia and one of the few published in Latinamerica. We are facing a chronic disease with a frequently delayed diagnosis, which is difficult to treat and affects quality of life. Is important to do an early intervention to improve the prognosis. Further studies are needed about HS main characteristics.

Evaluation of KRAS Concomitant Mutations in Advanced Lung Adenocarcinoma Patients.

Background and Objectives: One of the most frequently mutated oncogenes in cancer belongs to the Ras family of proto-oncogenes, which encode distinct key signaling events. RAS gain-of-function mutations are present in ~30% of all human cancers, with KRAS being the most frequently mutated isoform showing alterations in different cancer types including lung cancer. This study aimed to investigate the incidence of KRAS mutations, and concomitant mutations, in advanced non-small cell lung adenocarcinoma patients. Materials and Methods: This was a retrospective study, where genomic DNA extracted from paraffin-embedded tumor tissues from 121 Brazilian advanced non-small cell lung adenocarcinoma patients were analyzed to evaluate via Next Generation Sequencing (NGS) the incidence of KRAS mutations and co-occurring mutations and correlate, when possible, to clinicopathological characteristics. Statistical analyses were performed to calculate the prevalence of mutations and to investigate the association between mutational status, mutation type, and sex. Results: The results showed a prevalence of male (N = 63; 54.8%) compared to female patients (N = 52, 45.2%), and mutant KRAS was present in 20.86% (24/115) of all samples. Interestingly, 33.3% of the mutant KRAS samples showed other mutations simultaneously. Conclusions: This study revealed the presence of rare KRAS concomitant mutations in advanced lung adenocarcinoma patients. Further investigation on the importance of these genomic alterations in patient prognosis and treatment response is warranted.

Curcuma as an adjuvant in colorectal cancer treatment.

Colorectal cancer (CRC) is the second leading cause of cancer death worldwide and mostly affects men. Around 20% of its incidence is by familiar disposition due to hereditary syndromes. The CRC treatment involves surgery and chemotherapy; however, the side effects of treatments and the fast emergence of drug resistance evidence the necessity to find more effective drugs. Curcumin is the main polyphenol pigment present in Curcuma longa, a plant widely used as healthy food with antioxidant properties. Curcumin has synergistic effects with antineoplastics such as 5-fluorouracil and oxaliplatin, as well anti-inflammatory drugs by inhibiting cyclooxygenase-2 and the Nuclear factor kappa B. Furthermore, curcumin shows anticancer properties by inhibition of the Wnt/ß-catenin, Hedgehog, Notch, and the phosphatidylinositol-3-kinase (PI3K)/Akt and the mammalian target of rapamycin (mTOR) signaling pathways implicated in the progression of CRC. However, the consumption of pure curcumin is less suitable, as the absorption is poor, and the metabolism and excretion are high. Pharmacological formulations and essential oils of the plant improve the curcumin absorption, resulting in therapeutical dosages. Despite the evidence obtained in vitro and in vivo, clinical studies have not yet confirmed the therapeutic potential of curcumin against CRC. Here we reviewed the last scientific information that supports the consumption of curcumin as an adjuvant for CRC therapy.

Rationale of an Advanced Integrative Approach Applied to Autism Spectrum Disorder: Review, Discussion and Proposal.

The rationale of an Advanced Integrative Model and an Advanced Integrative Approach is presented. In the context of Allopathic Medicine, this model introduces the evaluation, clinical exploration, diagnosis, and treatment of concomitant medical problems to the diagnosis of Autism Spectrum Disorder. These may be outside or inside the brain. The concepts of static or chronic, dynamic encephalopathy and condition for Autism Spectrum Disorder are defined in this model, which looks at the response to the treatments of concomitant medical problemsto the diagnosis of Autism Spectrum Disorder. (1) Background: Antecedents and rationale of an Advanced Integrative Model and of an Advanced Integrative Approach are presented; (2) Methods: Concomitant medical problems to the diagnosis of Autism Spectrum Disorder and a discussion of the known responses of their treatments are presented; (3) Results: Groups in Autism are defined and explained, related to the responses of the treatments of the concomitant medical problems to ASD and (4) Conclusions: The analysis in the framework of an Advanced Integrative Model of three groups including the concepts of static encephalopathy; chronic, dynamic encephalopathy and condition for Autism Spectrum Disorder explains findings in the field, previously not understood.

Association between the level of attention and dual-task costs on postural sway and cognitive yield in children, adolescents, and young adults.

BACKGROUND: Postural stability requires attentional resources. Dual-task paradigms are used to investigate the attentional demand of the studied tasks. However, no studies have been conducted on the subjects' level of attention, analyzing its association with dual-task costs (DTC). RESEARCH QUESTION: To evaluate the attentional level and DTC on postural sway and cognitive yield in children, adolescents, and young adults, investigating age-related differences, and to analyze if the participants' attention level is associated with DTC. METHODS: Postural sway and cognitive-yield of 30 children, 24 adolescents, and 32 young adults were assessed in a dual-task paradigm. We calculated DTC on postural sway and cognitive yield. Attention level was tested using Psychological Battery for Attention Assessment. We tested the association between DTC and attention level. RESULTS: Young adults showed higher DTC on area and velocity of postural sway than children and adolescents. No differences in DTC on cognitive yield were found between the groups. Children showed lower attention levels than adolescents and young adults. Attention level was negatively associated with DTC on cognitive yield in young adults. Focused Attention is responsible for 24.4% of the variance in DTC on cognitive yield. CONCLUSION: Age impacts DTC on postural stability, but not on cognitive performance. The smaller changes in sway found in children/adolescents when dual-tasking, potentially reflect less developed attentional levels and postural control, which make them performing postural tasks closed to their stability boundaries, and, therefore, make them prioritize stability protection more than adults. Similar DTC on cognition between groups may reflect an equalization of the chosen cognitive task at everyone's difficulty level. The lower attention levels of children may reflect an attentional system in development, with prioritization o postural tasks when dual-tasking to maintain stability. Although attention level increases throughout age, attention only predicted DTC on cognition. Better Focused Attention's levels predicted lower DTC on cognitive yield for young adults.

Autologous Infusion of Bone Marrow and Mesenchymal Stromal Cells in Patients with Chronic Obstructive Pulmonary Disease: Phase I Randomized Clinical Trial.

BACKGROUND AND OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is characterized by the destruction of alveolar walls, chronic inflammation and persistent respiratory symptoms. There is no curative clinical treatment for COPD. In this context, cell-based therapy is a promising therapeutic alternative for COPD. Thus, in this open, controlled and randomized Phase I Clinical Trial, we aimed to assess the safety of the infusion of autologous bone marrow mononuclear cells (BMMC), adipose-derived mesenchymal stromal cells (ADSC) and, especially, the safety of concomitant infusion (co-infusion) of BMMC and ADSC as a new therapeutic alternative for COPD. The rationale for co-infusion of BMMC and ADSC is based on the hypothesis of an additive or synergistic therapeutic effect resulting from this association. METHODS: To achieve the proposed objectives, twenty patients with moderate-to-severe COPD were randomly divided into four groups: control group - patients receiving conventional treatment; BMMC group - patients receiving only BMMC; ADSC group - patients receiving only ADSC, and co-infusion group - patients receiving the concomitant infusion of BMMC and ADSC. Patients were assessed for pulmonary function, biochemical profile, and quality of life over a 12 months follow-up. RESULTS: No adverse events were detected immediately after the infusion of BMMC, ADSC or co-infusion. In the 12-month follow-up, no causal relationship was established between adverse events and cell therapy procedures. Regarding the efficacy, the BMMC group showed an increase in forced expiratory volume (FEV1) and diffusing capacity for carbon monoxide (DLCO). Co-infusion group showed a DLCO, and gas exchange improvement and a better quality of life. CONCLUSION: The results obtained allow us to conclude that cell-based therapy with co-infusion of BMMC and ADSC is a safe procedure and a promising therapeutic for COPD. However, additional studies with a greater number of patients are needed before randomized and controlled Phase III clinical trials can be implemented.

In vivo demonstration of immunologic cross-reactivity to octylisothiazolinone in patients primarily and strongly sensitized to methylisothiazolinone.

BACKGROUND: Notwithstanding that concomitant exposure to different isothiazolinone derivatives may result in concomitant sensitization, clinical and animal studies have suggested cross-reactivity between these derivatives, notably between methylisothiazolinone (MI) and octylisothiazolinone (OIT). OBJECTIVE: To investigate if patients sensitized to MI show cross-reactions to OIT and/or to benzisothiazolinone (BIT) by applying the concept of the re-test method. PATIENTS AND METHODS: From March to October 2019 consecutive patients were patch tested with MI 0.2% aqueous in duplicate at the two lower corners of both shoulder blades. Patients sensitized to MI, but not to OIT 0.1% petrolatum (pet.) nor to BIT 0.1% pet., were re-tested, 2 months later, with the latter two derivatives at the skin sites where the MI reactions had fully disappeared. RESULTS: Of 116 patients, 15 (13%) were sensitized to MI, eight of these not sensitized to BIT nor to OIT. Of these, seven patients, all (very) strongly sensitized to MI, were re-tested: five patients showed positive patch test reactions to OIT 0.1% pet.; one patient to OIT 0.1% pet. and BIT 0.1% pet.; and one other patient showed no reactions. CONCLUSION: This study suggests that patients primarily and strongly sensitized to MI may show immunologic cross-reactions to OIT, and to a far lesser extent to BIT.

177Lu-Bombesin-PLGA (paclitaxel): A targeted controlled-release nanomedicine for bimodal therapy of breast cancer.

The gastrin-releasing peptide receptor (GRPr) is overexpressed in >75% of breast cancers. 177Lu-Bombesin (177Lu-BN) has demonstrated the ability to target GRPr and facilitate efficient delivery of therapeutic radiation doses to malignant cells. Poly(d,l­lactide­co­glycolide) acid (PLGA) nanoparticles can work as smart drug controlled-release systems activated through pH changes. Considering that paclitaxel (PTX) is a first-line drug for cancer treatment, this work aimed to synthesize and chemically characterize a novel polymeric PTX-loaded nanosystem with grafted 177Lu-BN and to evaluate its performance as a targeted controlled-release nanomedicine for concomitant radiotherapy and chemotherapy of breast cancer. PLGA(PTX) nanoparticles were synthesized using the single emulsification-solvent evaporation method with PVA as a stabilizer in the presence of PTX. Thereafter, the activation of PLGA carboxylic groups for BN attachment through the Lys1-amine group was performed. Results of the chemical characterization by FT-IR, DLS, HPLC and SEM/TEM demonstrated the successful synthesis of BN-PLGA(PTX) with a hydrodynamic diameter of 163.54 ±â€¯33.25 nm. The entrapment efficiency of paclitaxel was 92.8 ±â€¯3.6%. The nanosystem showed an adequate controlled release of the anticancer drug, which increased significantly due to the pH change from neutral (pH = 7.4) to acidic conditions (pH = 5.3). After labeling with 177Lu and purification by ultrafiltration, 177Lu-BN-PLGA(PTX) was obtained with a radiochemical purity of 99 ±â€¯1%. In vitro and in vivo studies using MDA-MB-231 breast cancer cells (GRPr-positive) demonstrated a 177Lu-BN-PLGA(PTX) specific uptake and a significantly higher cytotoxic effect for the radiolabeled nanosystem than the unlabeled BN-PLGA(PTX) nanoparticles. Using a pulmonary micrometastasis MDA-MB-231 model, the added value of 177Lu-BN-PLGA(PTX) for tumor imaging was confirmed. The 177Lu-BN-PLGA(PTX) nanomedicine is suitable as a targeted paclitaxel delivery system with concomitant radiotherapeutic effect for the treatment of GRPr-positive breast cancer.

Monoclinic and orthorhombic forms of (RS)-(E)-4-[2-(4-chlorobenzylidene)hydrazinyl]-6,11-dimethyl-6,11-dihydro-5H-benzo[b]pyrimido[5,4-f]azepine: synthesis, concomitant polymorphism and supramolecular assembly mediated by C-H...N, C-H...π(arene) and C-Cl...π(arene) interactions.

The title compound, C21H20ClN5, has been synthesized in two steps from (RS)-4-chloro-6,11-dimethyl-6,11-dihydro-5H-benzo[b]pyrimido[5,4-f]azepine and characterized by 1H and 13C NMR spectroscopy and by high-resolution mass spectrometry. Crystallization from hexane-ethyl acetate yields approximately equal quantities of a monoclinic polymorph in the space group Cc, (I), and an orthorhombic polymorph in the space group Pna21, (II). The molecules in polymorphs (I) and (II) show small differences in their molecular conformations, particularly in the shape of the azepine ring and the orientation of the chlorophenyl substituent. The molecules in polymorph (I) are linked by C-H...N and C-H...π(arene) hydrogen bonds to form sheets, which are linked into a three-dimensional framework structure by C-Cl...π(arene) interactions. There are no C-Cl...π(arene) interactions between the molecules in polymorph (II) and the supramolecular assembly takes the form of sheets built from C-H...N and C-H...π(arene) hydrogen bonds. Comparisons are made with some related structures.