Glucose Deprivation Promotes Pseudohypoxia and Dedifferentiation in Lung Adenocarcinoma.

Increased utilization of glucose is a hallmark of cancer. Sodium-glucose transporter 2 (SGLT2) is a critical player in glucose uptake in early-stage and well-differentiated lung adenocarcinoma (LUAD). SGLT2 inhibitors, which are FDA approved for diabetes, heart failure, and kidney disease, have been shown to significantly delay LUAD development and prolong survival in murine models and in retrospective studies in diabetic patients, suggesting that they may be repurposed for lung cancer. Despite the antitumor effects of SGLT2 inhibition, tumors eventually escape treatment. Here, we studied the mechanisms of resistance to glucose metabolism-targeting treatments. Glucose restriction in LUAD and other tumors induced cancer cell dedifferentiation, leading to a more aggressive phenotype. Glucose deprivation caused a reduction in alpha-ketoglutarate (αKG), leading to attenuated activity of αKG-dependent histone demethylases and histone hypermethylation. The dedifferentiated phenotype depended on unbalanced EZH2 activity that suppressed prolyl-hydroxylase PHD3 and increased expression of hypoxia-inducible factor 1α (HIF1α), triggering epithelial-to-mesenchymal transition. Finally, a HIF1α-dependent transcriptional signature of genes upregulated by low glucose correlated with prognosis in human LUAD. Overall, this study furthers current knowledge of the relationship between glucose metabolism and cell differentiation in cancer, characterizing the epigenetic adaptation of cancer cells to glucose deprivation and identifying targets to prevent the development of resistance to therapies targeting glucose metabolism. SIGNIFICANCE: Epigenetic adaptation allows cancer cells to overcome the tumor-suppressive effects of glucose restriction by inducing dedifferentiation and an aggressive phenotype, which could help design better metabolic treatments.

Accuracy of frozen section remote subspecialty consultation using real-time telepathology and whole-slide imaging in gynecologic cases.

OBJECTIVES: Intrapathology consultation is recommended for complex cases during frozen section (FS) as routine practice. In our institution, solicited second opinions were traditionally provided by in-person consultation (IPC). Whole-slide imaging (WSI) was implemented in 2018 as an alternative but replaced by videoconferencing in 2020. Here, we assess the accuracy of remote FS consultation using these digital modalities vs IPC. METHODS: Gynecologic FS cases over a 4-year period overseen by 2 intraoperative consultants were grouped by consultation method: (1) IPC, (2) WSI, and (3) videoconferencing. Accuracy was determined by concordance between the FS and final report diagnoses. Turnaround time between the 3 groups was analyzed using SPSS statistical software (IBM). RESULTS: Using WSI and videoconferencing, 100% concordance was observed, while the IPC group had a 98.5% concordance rate. Videoconferencing, however, showed longer turnaround times (mean, 45.59 minutes) than IPC (mean, 33.36 minutes). Although turnaround time positively correlated with the number of FS specimens, blocks, and H&E slides per case, no statistically significant differences in the number of specimens, blocks, and H&E slides generated were found among the consultation methods. CONCLUSIONS: Even though turnaround time using videoconferencing is longer, the accuracy of WSI and videoconferencing for remote FS consultation is equivalent to IPC. It is therefore a safe method for conducting intrapathology FS consultation in challenging surgical cases.

Resistencia bacteriana a antibióticos en ambientes acuáticos: origen e implicaciones para la salud pública

El alarmante incremento de la resistencia bacteriana a los antibióticos a nivel global ha dilucidado otras fuentes diferentes al hospital y la comunidad, donde el agua ha cobrado gran importancia. El ambiente acuático constituye la fuente y el hábitat natural de un gran número de microorganismos, incluyendo bacterias resistentes a antibióticos; así mismo, se considera uno de los principales receptores de antimicrobianos, bacterias resistentes y genes de resistencia a antibióticos provenientes de las actividades humanas. La contaminación del agua con estos contaminantes emergentes tiene implicaciones serias para la salud humana, relacionadas con la diseminación de la resistencia bacteriana y la emergencia de nuevos mecanismos de resistencia. En esta revisión se brinda una descripción global del papel de los ambientes acuáticos en el problema de la resistencia bacteriana, las principales fuentes de contaminación, además del impacto para la salud pública. Ante este panorama, se establece la necesidad de abordar la problemática de la resistencia bacteriana desde la perspectiva de "una salud", donde a la vigilancia tradicional, enfocada a nivel humano y veterinario, se articule la vigilancia epidemiológica ambiental, principalmente basada en aguas residuales.

The alarming increase in bacterial resistance to antibiotics globally has diluted sources other than the hospital and community, where water has taken on great importance. The aquatic environment is the source and natural habitat of a large number of microorganisms, including antibiotic-resistant bacteria, as well as being considered one of the main receptors for antimicrobials, resistant bacteria and antibiotic resistance genes from human activities. Contamination of water with these emerging contaminants has serious implications for human health related to the spread of bacterial resistance and the emergence of new resistance mechanisms. This review provides a global description of the role of aquatic environments in the problem of bacterial resistance, the main sources of contamination, as well as the impact on Public Health. In this context, the need arises to address the problem of bacterial resistance from the perspective of "one health", where traditional surveillance, focused at the human and veterinary level, is articulated with environmental epidemiological surveillance, mainly in wastewater.

O incremento alarmante da resistência bacteriana aos antibióticos no nível global tem revelado outras fontes diferentes do hospital e da comunidade, em que a água tem ganho grande importância. O ambiente aquático constitui a fonte e o hábitat natural de um grande número de microrganismos, incluindo bactérias resistentes a antibióticos; é considerado, também, um dos principais receptores de antimicrobianos, bactérias resistentes e genes de resistência a antibióticos provindos das atividades humanas. A poluição da água com esses poluentes emergentes tem sérias implicações para a saúde humana, relacionadas com a disseminação da resistência bacteriana e a emergência de novos mecanismos de resistência. Nesta revisão oferece-se uma descrição global do papel dos ambientes aquáticos na situação problemática da resistência bacteriana, as principais fontes de poluição, além do impacto para a saúde pública. Diante desse panorama, determina-se a necessidade de abordar a problemática da resistência bacteriana desde a perspectiva de "uma saúde" em que a vigilância tradicional, focada nos níveis humano e veterinário, esteja articulada com a vigilância epidemiológica ambiental, principalmente baseada em águas residuais.

Lefort I Osteotomy With and Without Osteogenic Distraction in Cleft Lip and Palate Patients: Experience at Hospital Universitario Infantil De San José.

INTRODUCTION: Cleft lip and cleft palate (CLP) are congenital diseases that lead to several secondary craniofacial anomalies, such as hypoplasia of the middle third of the face, which can be treated with different surgical techniques to help improve functional and esthetic alterations associated with the maxilla. This article reports the results of patients managed with LeFort I osteotomy in the same craniofacial surgery center for 10 years. OBJECTIVE: To determine the postoperative results regarding recurrence rates, malocclusion, and speech status after surgical treatment, in patients with retrusion of the midface with CLP, who underwent LeFort I osteotomy with or without osteogenic distraction (OD). METHODS: A descriptive cohort study was performed at the Hospital Infantil Universitario de San José in Bogotá, Colombia, between 2010 and 2020, evaluating 38 patients with CLP who met the inclusion criteria, all managed by LeFort I osteotomy with and without OD. The authors reported the sociodemographic information, as well as data related to speech before and after surgery, recurrence, complications, and cephalometric characteristics. The recurrence of the patients was described at 6 and 12 months after the surgical procedure. RESULTS: A total of 43 patients met the inclusion criteria, of which 20 patients were managed with conventional LeFort I osteotomy, and 23 with LeFort I osteotomy with OD; 5 patients were excluded due to lack of data in the medical records, with a final sample of 38 patients. The distribution based on sex was: 57.8% men and 42.1% women. Regarding laterality, we have 7 patients with right CLP (18.42%), 11 patients with left CLP (28.9%), and 20 patients with bilateral CLP (52.63%), 100% of patients with a class III bite in Angle's classification. In group 1 (OD), 55% of the patients did not present changes in speech before surgery, 30% presented improvement in speech, and 15% worsened it. In group 2 (conventional advancement), 66% of the patients did not present changes in speech, 5.5% presented improvement, and 27.7% presented worsening of speech based on the preoperative condition, with a clinical recurrence at 6 months of 15% for group 1 and of 33% for group 2, and at 1 year of 20% for group 1 and 16% for group 2. CONCLUSIONS: Osteogenic distraction is a safe method that can be applied in patients with CLP depending on the clinical characteristics. According to what is described in the literature, those patients who require advancement of up to 6 mm treated without OD have obtained good results, showing esthetic improvement by increasing the projection of the middle third of the face, without worsening of velopharyngeal insufficiency and achieving an adequate occlusal class (Angle I) in the immediate postoperative period or after the postoperative orthodontic management. However, in patients who require advances ≥7 mm, it is clear that OD is the best option, given its association with a lower recurrence rate, minimal changes in the speech, achieving occlusion edge-to-edge at the end of the distraction or Angle's class I, which is corroborated by the results obtained in this study.

Biofortification of Broccoli Microgreens (Brassica oleracea var. italica) with Glucosinolates, Zinc, and Iron through the Combined Application of Bio- and Nanofertilizers.

There is a severe need to develop a sustainable, affordable, and nutritious food supply system. Broccoli microgreens have attracted attention due to their rich nutritional content and abundant bioactive compounds, constituting an important opportunity to feed the ever-increasing population and fight global health problems. This study aimed to measure the impact of the combined application of biofertilizers and zinc and iron nanofertilizers on plant growth and the biofortification of glucosinolates (GLSs) and micronutrients in broccoli microgreens. Biofertilizers were based on plant growth-promoting (PGP) bacterial consortia previously isolated and characterized for multiple PGP traits. Nanofertilizers consisted of ZnO (77 nm) and γ-Fe2O3 (68 nm) nanoparticles synthesized with the coprecipitation method and functionalized with a Pseudomonas species preparation. Treatments were evaluated under seedbed conditions. Plant growth parameters of plant height (37.0-59.8%), leaf diameter (57.6-81.1%) and fresh weight (112.1-178.0%), as well as zinc (122.19-363.41%) and iron contents (55.19-161.57%), were mainly increased by nanoparticles subjected to the functionalization process with Pseudomonas species and uncapped NPs applied together with the biofertilizer treatment. Regarding GLSs, eight compounds were detected as being most positively influenced by these treatments. This work demonstrated the synergistic interactions of applying ZnO and γ-Fe2O3 nanofertilizers combined with biofertilizers to enhance plant growth and biofortify micronutrients and glucosinolates in broccoli microgreens.

Tailoring pretext tasks to improve self-supervised learning in histopathologic subtype classification of lung adenocarcinomas.

Lung adenocarcinoma (LUAD) is a morphologically heterogeneous disease with five predominant histologic subtypes. Fully supervised convolutional neural networks can improve the accuracy and reduce the subjectivity of LUAD histologic subtyping using hematoxylin and eosin (H&E)-stained whole slide images (WSIs). However, developing supervised models with good prediction accuracy usually requires extensive manual data annotation, which is time-consuming and labor-intensive. This work proposes three self-supervised learning (SSL) pretext tasks to reduce labeling effort. These tasks not only leverage the multi-resolution nature of the H&E WSIs but also explicitly consider the relevance to the downstream task of classifying the LUAD histologic subtypes. Two tasks involve predicting the spatial relationship between tiles cropped from lower and higher magnification WSIs. We hypothesize that these tasks induce the model to learn to distinguish different tissue structures presented in the images, thus benefiting the downstream classification. The third task involves predicting the eosin stain from the hematoxylin stain, inducing the model to learn cytoplasmic features relevant to LUAD subtypes. The effectiveness of the three proposed SSL tasks and their ensemble was demonstrated by comparison with other state-of-the-art pretraining and SSL methods using three publicly available datasets. Our work can be extended to any other cancer type where tissue architectural information is important. The model could be used to expedite and complement the process of routine pathology diagnosis tasks. The code is available at https://github.com/rina-ding/ssl_luad_classification.

Ecophysiology of neotropical amphibians and reptiles: lessons learned from Colombia.

Ecophysiology and herpetology share a close historical relationship, but earlier work at the interface of these disciplines was carried out in temperate regions. Tropical regions like the Neotropics exhibit the highest species richness for amphibians and reptiles, but the pace for ecophysiological research on tropical herpetofauna has been slower relative to temperate counterparts. We are a group of early-career, Latin American researchers interested in the physiological diversity exhibited by neotropical herpetofauna. As such, we have engaged in the organization of the Symposium on the Ecophysiology of Neotropical Amphibians and Reptiles (ECOPHYSHERP) to integrate the scientific community interested on these topics. ECOPHYSHERP has been held three times already within the Colombian Congress of Herpetology, and collectively it has hosted >60 contributions from researchers at 26 institutions and eight countries. Participation has been diverse in terms of gender, age, and career stage, but most participants have been young undergraduate biology students. This generation of early-career researchers is producing excellent research in a broad range of topics, but difficulties to convert this research into scientific publications may exist. Identifying and contributing in order to solve such problems are priorities for this organizing committee, and also our endeavours towards ECOPHYSHERP 4.0 in Santa Marta in 2025.

"Copy number alteration" as the sole molecular finding of a Thyroseq test is more commonly seen in Hurthle cell neoplasms.

BACKGROUND: To better understand the molecular alterations associated with Hurthle cell lesions of the thyroid, we retrospectively reviewed the association of clonal DNA copy number alterations (CNAs) with fine needle aspiration (FNA) cytomorphology and surgical follow-up. METHODS: Hurthle cell type (HCT) and non-Hurthle cell type (NHCT) thyroid FNAs that were classified according to the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) as atypia of undetermined significance (AUS) and suspicious for a follicular neoplasm (SFN) with corresponding molecular testing performed by ThyroSeq v3 genomic classifier were compared to surgical follow-up. RESULTS: A total of 54 thyroid FNA cases were identified, distributed among the following categories: AUS-HCT (n = 15, 27.8%), SFN-HCT (n = 11, 20.4%), AUS-NHCT (n = 19, 35.2%), and SFN-NHCT (n = 9, 16.6%). The lesions classified as AUS-HCT and SFN-HCT showed a higher prevalence of CNAs (n = 10/26; 38.5%) compared to their NHCT counterparts (n = 3/28; 10.7%) (p < .03). Of the 42 patients (77.8%) with surgical follow-up, CNAs were more often seen in benign (n = 10/26, 38.5%) than malignant conditions (n = 1/16, 6.3%) (p < .03). CNAs were encountered in more lesions with Hurthle cell features on histologic examination (n = 8/14, 57.1%) than those without (n = 3/28, 10.7%) (p < .002). The presence of CNAs alone was seen only in benign adenomas and more commonly with Hurthle cell features (n = 5/7, 71.4%). CONCLUSION: In this study, CNAs were associated with Hurthle cell morphology on thyroid FNA and benign adenomas upon surgical follow-up. Therefore, if the only finding of a positive ThyroSeq v3 GC result is a CNA, conservative management can be considered if clinically indicated.

Cytokine signaling converging on IL11 in ILD fibroblasts provokes aberrant epithelial differentiation signatures.

Introduction: Interstitial lung disease (ILD) is a heterogenous group of lung disorders where destruction and incomplete regeneration of the lung parenchyma often results in persistent architectural distortion of the pulmonary scaffold. Continuous mesenchyme-centered, disease-relevant signaling likely initiates and perpetuates the fibrotic remodeling process, specifically targeting the epithelial cell compartment, thereby destroying the gas exchange area. Methods: With the aim of identifying functional mediators of the lung mesenchymal-epithelial crosstalk with potential as new targets for therapeutic strategies, we developed a 3D organoid co-culture model based on human induced pluripotent stem cell-derived alveolar epithelial type 2 cells that form alveolar organoids in presence of lung fibroblasts from fibrotic-ILD patients, in our study referring to cases of pulmonary fibrosis, as well as control cell line (IMR-90). Results: While organoid formation capacity and size was comparable in the presence of fibrotic-ILD or control lung fibroblasts, metabolic activity was significantly increased in fibrotic-ILD co-cultures. Alveolar organoids cultured with fibrotic-ILD fibroblasts further demonstrated reduced stem cell function as reflected by reduced Surfactant Protein C gene expression together with an aberrant basaloid-prone differentiation program indicated by elevated Cadherin 2, Bone Morphogenic Protein 4 and Vimentin transcription. To screen for key mediators of the misguided mesenchymal-to-epithelial crosstalk with a focus on disease-relevant inflammatory processes, we used mass spectrometry and characterized the secretome of end stage fibrotic-ILD lung fibroblasts in comparison to non-chronic lung disease (CLD) patient fibroblasts. Out of the over 2000 proteins detected by this experimental approach, 47 proteins were differentially abundant comparing fibrotic-ILD and non-CLD fibroblast secretome. The fibrotic-ILD secretome profile was dominated by chemokines, including CXCL1, CXCL3, and CXCL8, interfering with growth factor signaling orchestrated by Interleukin 11 (IL11), steering fibrogenic cell-cell communication, and proteins regulating extracellular matrix remodeling including epithelial-to-mesenchymal transition. When in turn treating alveolar organoids with IL11, we recapitulated the co-culture results obtained with primary fibrotic-ILD fibroblasts including changes in metabolic activity. Conclusion: We identified mediators likely contributing to the disease-perpetuating mesenchymal-to-epithelial crosstalk in ILD. In our alveolar organoid co-cultures, we were able to highlight the importance of fibroblast-initiated aberrant epithelial differentiation and confirmed IL11 as a key player in fibrotic-ILD pathogenesis by unbiased fibroblast secretome analysis.

Emerging Diabetes Technologies: Continuous Glucose Monitors/Artificial Pancreases.

Over the past decade there have been many advances in diabetes technologies, such as continuous glucose monitors (CGM s), insulin-delivery devices, and hybrid closed loop systems . Now most CGMs (Medtronic-Guardian, Dexcom-G6, and Abbott-Libre-2) have MARD values of < 10%, in contrast to two decades ago when the MARD used to be > 20%. In addition, the majority of the new CGMs do not require calibrations, and the latest CGMs last for 10-14 days. An implantable 6-months CGM by Eversense-3 is now approved in the USA and Europe. Recently, the FDA approved Libre 3 which provides real-time glucose values every minute. Even though it is approved as an iCGM it is not interoperable with automatic-insulin-delivery (AID) systems. The newer CGMs that are likely to be launched in the next few months in the USA include the 10-11 days Dexcom G7 (60% smaller than the existing G6), and the 7-days Medtronic Guardian 4. Most of the newer CGM have several features like automatic initialization, easy insertion, predictive alarms, and alerts. It has also been noticed that an arm insertion site might have better accuracy than abdomen or other sites, like the buttock for kids. Lag time between YSI and different sensors have been reported differently, sometimes it is down to 2-3 min; however, in many instances, it is still 15-20 min, especially when the rate of change of glucose is > 2 mg/min. We believe that in the next decade there will be a significant increase in the number of people who use CGM for their day-to-day diabetes care.

Corrigendum: Monocyte signature as a predictor of chronic lung disease in the preterm infant.

[This corrects the article DOI: 10.3389/fimmu.2023.1112608.].

Monocyte signature as a predictor of chronic lung disease in the preterm infant.

Introduction: Inflammation is a key driver of morbidity in the vulnerable preterm infant exposed to pre- and postnatal hazards and significantly contributes to chronic lung disease, i.e. bronchopulmonary dysplasia (BPD). However, the early changes in innate immunity associated with BPD development are incompletely understood. Methods: In very immature preterm infants below 32 weeks gestational age (GA; n=30 infants), monocyte subtypes were identified by Flow Cytometry at birth and throughout the postnatal course including intracellular TNF expression upon LPS stimulation. Complementing these measurements, cytokine end growth factor expression profiles (Luminex® xMAP®; n=110 infants) as well as gene expression profiles (CodeLinkTM Human I Bioarray; n=22) were characterized at birth. Results: The abundance of monocyte subtypes differed between preterm and term neonates at birth. Specifically, CD14++CD16+ (intermediate) monocytes demonstrated a dependency on PMA and elevated levels of nonclassical (CD14+CD16++) monocytes characterized preterm infants with developing BPD. Postnatally, lung injury was associated with an increase in intermediate monocytes, while high levels of nonclassical monocytes persisted. Both subtypes were revealed as the main source of intracellular TNF-α expression in the preterm infant. We identified a cytokine and growth factor expression profile in cord blood specimen of preterm infants with developing BPD that corresponded to the disease-dependent regulation of monocyte abundances. Multivariate modeling of protein profiles revealed FGF2, sIL-2 Rα, MCP-1, MIP1a, and TNF-α as predictors of BPD when considering GA. Transcriptome analysis demonstrated genes predicting BPD to be overrepresented in inflammatory pathways with increased disease severity characterized by the regulation of immune and defense response pathways and upstream regulator analysis confirmed TNF-α, interleukin (IL) -6, and interferon α as the highest activated cytokines in more severe disease. Whereas all BPD cases showed downstream activation of chemotaxis and activation of inflammatory response pathways, more severe cases were characterized by an additional activation of reactive oxygen species (ROS) synthesis. Discussion: In the present study, we identified the early postnatal presence of nonclassical (CD14+CD16++) and intermediate (CD14++CD16+) monocytes as a critical characteristic of BPD development including a specific response pattern of monocyte subtypes to lung injury. Pathophysiological insight was provided by the protein and transcriptome signature identified at birth, centered around monocyte and corresponding granulocyte activation and highlighting TNFα as a critical regulator in infants with developing BPD. The disease severity-dependent expression patterns could inform future diagnostic and treatment strategies targeting the monocytic cell and its progeny.

Glucose deprivation promotes pseudo-hypoxia and de-differentiation in lung adenocarcinoma.

Increased utilization of glucose is a hallmark of cancer. Several studies are investigating the efficacy of glucose restriction by glucose transporter blockade or glycolysis inhibition. However, the adaptations of cancer cells to glucose restriction are unknown. Here, we report the discovery that glucose restriction in lung adenocarcinoma (LUAD) induces cancer cell de-differentiation, leading to a more aggressive phenotype. Glucose deprivation causes a reduction in alpha-ketoglutarate (αKG), leading to attenuated activity of αKG-dependent histone demethylases and histone hypermethylation. We further show that this de-differentiated phenotype depends on unbalanced EZH2 activity, causing inhibition of prolyl-hydroxylase PHD3 and increased expression of hypoxia inducible factor 1α (HIF1α), triggering epithelial to mesenchymal transition. Finally, we identified an HIF1α-dependent transcriptional signature with prognostic significance in human LUAD. Our studies further current knowledge of the relationship between glucose metabolism and cell differentiation in cancer, characterizing the epigenetic adaptation of cancer cells to glucose deprivation and identifying novel targets to prevent the development of resistance to therapies targeting glucose metabolism.

Barriers to and Outcomes of Initiating Clinical Research at Two Trauma Centers in Mexico.

INTRODUCTION: Despite efforts to advance clinical research through collaboration between Latin and North American partners, there remains persistent barriers to performing investigative work. To overcome these obstacles, a team of over 100 surgeon-leaders from 18 Latin American countries founded the Asociación de Cirujanos Traumatólogos de las Américas (ACTUAR). One of ACTUAR's first major collaborative projects, initiated in 2018, was a prospective, observational, multicenter study evaluating quality of life after open tibia fracture management. The current study identified common barriers experienced during the initiation of this study, as exemplified through two sites in Mexico. The study aims to identify obstacles to proactively overcome these in future collaborative work. METHODS: Two research assistants from University of California, San Francisco and two research coordinators from Mexico were recruited to share their experiences, identify common barriers experienced during site enrollment and on-boarding for the ACTUAR open tibia study, and discuss possible solutions. RESULTS: Barriers were organized into three categories: structural, logistical, and intrapersonal. Structural barriers included differences in patient populations and resources between private and public hospitals. Logistical barriers included ambiguous ethical review processes, internet availability, and low patient follow-up. Primary enrollment as a resident responsibility led to some intrapersonal barriers. Potential solutions were identified for each barrier and agreed upon by all collaborators. CONCLUSIONS: Multiple barriers were identified by research personnel who initiated a prospective surgical clinical research study in Mexico. Through collaborative approaches, many potential solutions may help overcome these barriers and build locally led research capacity in Latin America.

Clinical history of female-to-male transgender patients is needed to avoid misinterpretation of cervical Papanicolaou tests.

OBJECTIVE: Cervical cancer screening is as important in female-to-male transgender (FTMT) patients as it is in cisgender female patients. The aim of this study was to examine the impact of clinical information regarding gender identity and testosterone therapy on the cytological interpretations. METHODS: A list of FTMT patients and cisgender female patients who had received a cervical Papanicolaou (Pap) test for cancer screening was obtained. The cytological diagnoses, rendered at the time of collection, were recorded. A retrospective slide review with knowledge of the pertinent clinical information, including testosterone therapy status, was performed. The data sets were statistically compared. RESULTS: Of 122 cervical Pap tests in 111 FTMT individuals, 23 (19%) had surgical follow-ups; 73 (60%) had HPV testing, of which 12 (16%) were positive for high-risk strains; and 79 (65%) were known to be receiving testosterone. On the "original" review, 12 (9.8%) tests were diagnosed as unsatisfactory. Seventy-one (58%) Pap tests were initially diagnosed as negative for intraepithelial lesion or malignancy (NILM) without atrophy and 32 (26%) with atrophy. Seven (5.7%) of the tests were initially diagnosed as abnormal. On the "retrospective" review, the rate of unsatisfactory tests remained the same, and atrophy was observed in 76 (62%) tests. The number of abnormal tests was reduced to 4 (3.3%) after the retrospective review. Almost all comparative studies returned a P-value of ≤0.05. CONCLUSION: Our findings indicate that clinical information regarding whether a subject is transgender and/or is receiving testosterone therapy is crucial to avoiding Pap test overcalls.

Concern levels of beta-lactamase-producing Gram-negative bacilli in hospital wastewater: hotspot of antimicrobial resistance in Latin-America.

Hospital wastewater (HWW) discharges are among the main sources of antibiotic-resistant bacteria. This study detected a high frequency of beta-lactamase-producing Gram-negative Bacilli in HWW of different geographical regions of Colombia, even in the presence of the wastewater treatment plant, highlighting the importance of regulating these environments in developing countries.

Digital Global Recruitment for Women's Health Research: Cross-sectional Study.

BACKGROUND: With the increased popularity of mobile menstrual tracking apps and boosted Facebook posts, there is a unique opportunity to recruit research study participants from across the globe via these modalities to evaluate women's health. However, no studies to date have assessed the feasibility of using these recruitment sources for epidemiological research on ovulation and menstruation. OBJECTIVE: The objective of this study was to assess the feasibility of recruiting a diverse sample of women to an epidemiological study of ovulation and menstruation (OM) health (OM Global Health Study) using digital recruitment sources. The feasibility and diversity were assessed via click and participation rates, geographic location, BMI, smoking status, and other demographic information. METHODS: Participants were actively recruited via in-app messages using the menstrual tracking app Clue (BioWink GmbH) and a boosted Facebook post by DivaCup (Diva International Inc.). Other passive recruitment methods also took place throughout the recruitment period (eg, email communications, blogs, other social media). The proportion of participants who visited the study website after viewing and clicking the hypertext link (click rates) in the in-app messages and boosted Facebook post and the proportion of participants who completed the surveys per the number of completed consent and eligibility screeners (participation rates) were used to quantify the success of recruiting participants to the study website and study survey completion, respectively. Survey completion was defined as finishing the pregnancy and birth history section of the OM Global Health Study questionnaire. RESULTS: The recruitment period was from February 27, 2018, through January 24, 2020. In-app messages and the boosted Facebook post were seen by 104,000 and 21,400 people, respectively. Overall, 215 participants started the OM Global Health Study survey, of which 140 (65.1%), 39 (18.1%), and 36 (16.8%) participants were recruited via the app, the boosted Facebook post, and other passive recruitment methods, respectively. The click rate via the app was 18.9% (19,700 clicks/104,000 ad views) and 1.6% via the boosted Facebook post (340 clicks/21,400 ad views.) The overall participation rate was 44.6% (198/444), and the average participant age was 21.8 (SD 6.1) years. In terms of geographic and racial/ethnic diversity, 91 (44.2%) of the participants resided outside the United States and 147 (70.7%) identified as non-Hispanic White. In-app recruitment produced the most geographically diverse stream, with 44 (32.8%) of the 134 participants in Europe, 77 (57.5%) in North America, and 13 (9.8%) in other parts of the world. Both human error and nonhuman procedural breakdowns occurred during the recruitment process, including a computer programming error related to age eligibility and a hacking attempt by an internet bot. CONCLUSIONS: In-app messages using the menstrual tracking app Clue were the most successful method for recruiting participants from many geographic regions and producing the greatest numbers of started and completed surveys. This study demonstrates the utility of digital recruitment to enroll participants from diverse geographic locations and provides some lessons to avoid technical recruitment errors in future digital recruitment strategies for epidemiological research.

Presence of Human Papillomavirus DNA in Malignant Neoplasia and Non-Malignant Breast Disease.

Breast cancer is the leading cause of cancer death among women worldwide. Multiple extrinsic and intrinsic factors are associated with this disease's development. Various research groups worldwide have reported the presence of human papillomavirus (HPV) DNA in samples of malignant breast tumors. Although its role in mammary carcinogenesis is not fully understood, it is known that the HPV genome, once inserted into host cells, has oncogenic capabilities. The present study aimed to detect the presence of HPV DNA in 116 breast tissue biopsies and classify them according to their histology. It was found that 50.9% of the breast biopsies analyzed were malignant neoplasms, of which 74.6% were histologically classified as infiltrating ductal carcinoma. In biopsies with non-malignant breast disease, fibroadenoma was the most common benign neoplasm (39.1%). Detection of HPV DNA was performed through nested PCR using the external primer MY09/11 and the internal primer GP5+/6+. A hybridization assay genotyped HPV. HPV DNA was identified in 20.3% (12/59) of malignant neoplasms and 35% non-malignant breast disease (16/46). It was also detected in 27.3% (3/11) of breast tissue biopsies without alteration. However, there are no statistically significant differences between these groups and the existence of HPV DNA (p = 0.2521). Its presence was more frequent in non-malignant alterations than in malignant neoplasias. The most frequent genotypes in the HPV-positive samples were low-risk (LR) HPV-42 followed by high-risk (HR) HPV-31.