Inhibition of Multifunctional Protein p32/C1QBP Promotes Cytostatic Effects in Colon Cancer Cells by Altering Mitogenic Signaling Pathways and Promoting Mitochondrial Damage.

The protein p32 (C1QBP) is a multifunctional and multicompartmental homotrimer that is overexpressed in many cancer types, including colon cancer. High expression levels of C1QBP are negatively correlated with the survival of patients. Previously, we demonstrated that C1QBP is an essential promoter of migration, chemoresistance, clonogenic, and tumorigenic capacity in colon cancer cells. However, the mechanisms underlying these functions and the effects of specific C1QBP protein inhibitors remain unexplored. Here, we show that the specific pharmacological inhibition of C1QBP with the small molecule M36 significantly decreased the viability rate, clonogenic capacity, and proliferation rate of different colon cancer cell lines in a dose-dependent manner. The effects of the inhibitor of C1QBP were cytostatic and non-cytotoxic, inducing a decreased activation rate of critical pro-malignant and mitogenic cellular pathways such as Akt-mTOR and MAPK in RKO colon cancer cells. Additionally, treatment with M36 significantly affected the mitochondrial integrity and dynamics of malignant cells, indicating that p32/C1QBP plays an essential role in maintaining mitochondrial homeostasis. Altogether, our results reinforce that C1QBP is an important oncogene target and that M36 may be a promising therapeutic drug for the treatment of colon cancer.

Mutant p53 gain-of-function stimulates canonical Wnt signaling via PI3K/AKT pathway in colon cancer.

Aberrant canonical Wnt signaling is a hallmark of colon cancer. The TP53 tumor suppressor gene is altered in many solid tumors, including colorectal cancer, resulting in mutant versions of p53 (mut-p53) that lose their tumor suppressor capacities and acquire new-oncogenic functions (GOFs) critical for disease progression. Although the mechanisms related to mut-p53 GOF have been explored extensively, the relevance of mut-p53 in the canonical Wnt pathway is not well defined. This work investigated the influence of mut-p53 compared to wt-p53 in ß-catenin-dependent Wnt signaling. Using the TCGA public data from Pan-Cancer and the GEPIA2 platform, an in silico analysis of wt-p53 versus mut-p53 genotyped colorectal cancer patients showed that TP53 (p53) and CTNNB1 (ß-catenin) are significantly overexpressed in colorectal cancer, compared with normal tissue. Using p53 overexpression or p53 knockdown assays of wt-p53 or mut-p53, we found that while wt-p53 antagonizes canonical Wnt signaling, mut-p53 induces the opposite effect, improving the ß-catenin-dependent transcriptional activity and colony formation ability of colon cancer cells, which were both decreased by mut-p53 knockdown expression. The mechanism involved in mut-p53-induced activation of canonical Wnt appears to be via AKT-mediated phosphorylation of Ser 552 of ß-catenin, which is known to stabilize and enhance its transcriptional activity. We also found that while wt-p53 expression contributes to 5-FU sensitivity in colon cancer cells, the RITA p53 reactivating molecule counteracted the resistance against 5-FU in cells expressing mut-p53. Our results indicate that mut-p53 GOF acts as a positive regulator of canonical Wnt signaling and participates in the induction of resistance to 5-FU in colon cancer cells.

Top-down circuitry from the anterior insular cortex to VTA dopamine neurons modulates reward-related memory.

The insular cortex (IC) has been linked to the processing of interoceptive and exteroceptive signals associated with addictive behavior. However, whether the IC modulates the acquisition of drug-related affective states by direct top-down connectivity with ventral tegmental area (VTA) dopamine neurons is unknown. We found that photostimulation of VTA terminals of the anterior insular cortex (aIC) induces rewarding contextual memory, modulates VTA activity, and triggers dopamine release within the VTA. Employing neuronal recordings and neurochemical and transsynaptic tagging techniques, we disclose the functional top-down organization tagging the aIC pre-synaptic neuronal bodies and identifying VTA recipient neurons. Furthermore, systemic administration of amphetamine altered the VTA excitability of neurons modulated by the aIC projection, where photoactivation enhances, whereas photoinhibition impairs, a contextual rewarding behavior. Our study reveals a key circuit involved in developing and retaining drug reward-related contextual memory, providing insight into the neurobiological basis of addictive behavior and helping develop therapeutic addiction strategies.

Effect of the Addition of Fique Bagasse Cellulose Nanoparticles on the Mechanical and Structural Properties of Plastic Flexible Films from Cassava Starch.

One of the activities most representative of the agricultural sector in Colombia is the production of biodegradable fique fiber. The efficiency of the defiberization process of the fique leaves is very low since a mere 4% of the total weight of the leaf (cabuya) is used and marketed. The remaining 96%, composed of fique juice and bagasse, is considered to be waste and discarded, impacting the environment. The aim of this work was to study fique bagasse as a source of cellulose nanoparticles (CNCs). CNCs were obtained by acid hydrolysis and added at 10% to films made from cassava thermoplastic starch (TPS) by the casting method. Structural changes in the CNCs, TPS, and their mixtures were characterized by FTIR-ATR and their morphology and particle size by SEM and TEM microscopy, respectively. Thermal properties were analyzed using DSC and TGA, along with their effect on mechanical properties. Changes in the FTIR spectra indicated that the chemical method adequately removed hemicellulose and lignin from the fiber surface of fique bagasse. The CNCs showed a diameter and length of 7.5 ± 3.9 and 52.7 ± 18.1 nm, respectively, and TPS 10% CNC obtained an increase in mechanical strength of 116%. The obtainment of CNCs from lignocellulosic materials can thus be viewed as a favorable option for the subsequent reinforcement of a polymeric matrix.

Dietary Patterns of Children from the Amazon Region of Ecuador: A Descriptive, Qualitative Investigation.

Many young children in Ecuador suffer from high rates of malnutrition and stunting that affect their long-term growth and development. Little is known about the dietary patterns of children from the Amazon region who experience some of the highest rates of stunting (height-for-age) within Ecuador. Semi-structured interviews were conducted with 50 mothers of young children living in the Ecuadorian Amazon. In addition to descriptions of overall dietary patterns, three themes emerged from the interviews relating to strengths mothers have in feeding their children healthy diets: knowledge, autonomous and independent children, and supportive and responsive parenting. Five themes were found relating to barriers mothers have in feeding their children healthy diets. The first four themes concerned barriers (lack of knowledge of healthy foods, lack of access to healthy foods, not enough money, and child's health) related to multidimensional poverty. All these influenced the last theme found, namely, how difficult of an eater the child was. The implications of intervention efforts to reduce undernutrition and promote children's development by building on specific family and community strengths and identified barriers are also discussed in this paper.

Neutrophilic fixed drug eruption, a histopathologic variant or an expected finding?-A report of two cases and review of the literature.

Fixed drug eruption (FDE) is an adverse drug reaction characterized by recurrent circumscribed lesions at the same location upon re-exposure to the culprit medication, resulting in distinct postinflammatory hyperpigmentation. Histopathologically, FDE demonstrates a predominantly lymphocytic interface or lichenoid infiltrate with basal cell vacuolar changes and keratinocyte dyskeratosis/apoptosis. The term "neutrophilic fixed drug eruption" has been used to describe cases in which the inflammatory infiltrate is predominantly neutrophilic. The infiltrate can extend deeper in the dermis, potentially mimicking a neutrophilic dermatosis such as Sweet syndrome. We present two cases and review the literature to discuss the possibility that a neutrophilic inflammatory infiltrate may be an expected finding in FDE, rather than a histopathologic variant.

Effectiveness of Virtual Reality in Balance Training for Fall Prevention in Older Adults: Systematic Review.

OBJECTIVE: The purpose of this study was to determine the effectiveness of virtual reality (VR) in balance training for the prevention of falls in older adults. METHODS: We included studies with experimental designs, cohort studies, and quasi-experimental studies of older adults who underwent balance training associated with the use of VR for the prevention of falls. The comparison of control and intervention groups in the studies reported statistically significant improvements in terms of balance for VR. RESULTS: The effects and benefits from the use of VR were seen by the fourth week of intervention, with significant improvements in balance and lower fall rates, the improvements became greater for groups using VR. CONCLUSIONS: The benefits presented by the studies were related not only to balance but also to fear of falling, reaction time, gait, physical fitness, independence in activities of daily living, muscle strength, and even quality of life.

Non-canonical Wnt/Ca2+ signaling is essential to promote self-renewal and proliferation in colon cancer stem cells.

Introduction: Cancer Stem Cells (CSC) are responsible for maintaining tumor growth, chemoresistance, and metastasis. Therefore, understanding their characteristics is critical to progress in cancer therapy. While the contribution of the canonical Wnt/b-catenin signaling in both normal and CSCs had been well established, the function of non-canonical Wnt signaling cascades in stem cells is unclear. Recently, we reported that Wnt ligands trigger complex signaling in which the canonical and non-canonical responses can be simultaneously activated by one ligand in colon cancer cells, suggesting, therefore, that noncanonical Wnt pathways may also be important in CSCs. Methods: The present work aimed to know the role of the Wnt/Ca2+ pathway in colon CSCs. We used tumorspheres as a model of CSCs enrichment of CRC cell lines with different Wnt/b-catenin contexts. Results: Using Wnt3a and Wnt5a as prototype ligands to activate the canonical or the non-canonical pathways, respectively, we found that both Wnt3a and Wnt5a promote sphere-formation capacity and proliferation without stimulating b-catenin-dependent transcription. Upregulation of sphere formation by Wnt5a or Wnt3a requires the downstream activation of Phospholipase C and transcriptional factor NFAT. Moreover, the single specific inhibition of PLC or NFAT, using U73122 and 11R-VIVIT, respectively, leads to impaired sphere formation. Discussion: Our results indicate that both types of ligands activate the Wnt/Ca2+ signaling axis to induce/maintain the self-renewal efficiency of CSCs, demonstrating to be essential for the functions of CSC in colon cancer.

Salience to remember: VTA-IC dopaminergic pathway activity is necessary for object recognition memory formation.

Previous studies have shown that dopaminergic activity modulates the salience of novel stimuli enabling the formation of recognition memories. In this work, we hypothesize that dopamine released into the insular cortex (IC) from the ventral tegmental area (VTA) inputs enables the acquisition to consolidate object recognition memory. It has been reported that short training produces weak recognition memories; on the contrary, longer training produces lasting and robust recognition memories. Using a Cre-recombinase under the tyrosine hydroxylase (TH+) promoter mouse model, we photostimulated the VTA-IC dopaminergic pathway during short training or photoinhibited the same pathway during long training while mice explored objects. Our results showed that the photostimulation of the VTA-IC pathway during a short training enables the acquisition of recognition memory. Conversely, photoinhibition of the same pathway during a long training prevents the acquisition of recognition memory. Interestingly, the exploration time of the objects under photoinhibition or photostimulation of the dopaminergic VTA-IC pathway was not altered. Significantly, this enhancement of acquisition of the object recognition memory through the photostimulation of the VTA dopaminergic neurons could be impaired by the blockage of the D1-like receptors into the IC, either before or after the photostimulation. Altogether, our results suggest that dopamine released by the VTA is required during the acquisition to consolidate the object recognition memory through D1-like receptors into the IC without affecting the activity or the motivation to explore objects.

Reactive infectious mucocutaneous eruption due to COVID-19 with erythema-multiforme-like lesions and myeloid cells.

Reactive infectious mucocutaneous eruption (RIME) is a recently described entity in which there is prominent mucositis, most commonly involving the oral and urogenital mucosa, secondary to a variety of pathogens. There is typically minimal cutaneous involvement in RIME. This contrasts with erythema multiforme (EM) in which characteristic targetoid lesions predominate, usually in isolation (EM minor), but in a subset of cases, with severe mucositis (EM major). While the histopathologic features of RIME have not been as well defined, those of EM are characterized by epidermal apoptosis and interface dermatitis with lymphocytes making up the predominant cell type. We report a unique case of RIME in a 16-year-old male with COVID-19 characterized by significant mucositis involving the oral and genital mucosa, as well as numerous targetoid lesions on the trunk and extremities. Histopathologically, there was an inflammatory infiltrate obscuring and disrupting the epidermal interface, associated with epidermal necrosis, and blister formation. The infiltrate was composed of cells with irregular, non-segmented and elongate nuclei, with myeloid and histiocytoid cytomorphology. The cells were positive for myeloperoxidase, CD68, and CD163 (subset) suggesting myeloid lineage. RIME is a rarely reported COVID-19-related eruption, and targetoid lesions and myeloid interface reactions have not been described with RIME.

Modified Curcumins as Potential Drug Candidates for Breast Cancer: An Overview.

Breast cancer (BC), the most common malignancy in women, results from significant alterations in genetic and epigenetic mechanisms that alter multiple signaling pathways in growth and malignant progression, leading to limited long-term survival. Current studies with numerous drug therapies have shown that BC is a complex disease with tumor heterogeneity, rapidity, and dynamics of the tumor microenvironment that result in resistance to existing therapy. Targeting a single cell-signaling pathway is unlikely to treat or prevent BC. Curcumin (a natural yellow pigment), the principal ingredient in the spice turmeric, is well-documented for its diverse pharmacological properties including anti-cancer activity. However, its clinical application has been limited because of its low solubility, stability, and bioavailability. To overcome the limitation of curcumin, several modified curcumin conjugates and curcumin mimics were developed and studied for their anti-cancer properties. In this review, we have focused on the application of curcumin mimics and their conjugates for breast cancer.

El Instituto de Física de La Plata en la primera posguerra: la transmisión calificada de las ciencias a la juventud / The institute of physics of la plata in the first post-war period: the qualified transmission of sciences to young people

En la primera década del siglo XX la Universidad Nacional de La Plata, fundada en 1905, creó un moderno y bien dotado Instituto de Física. En este trabajo estudiamos el impacto que esa iniciativa tuvo sobre la modernización de la enseñanza de la física a nivel medio y universitario en la Argentina. Nos concentramos en dos de los egresados más representativos del Instituto de aquellos años, Ramón G. Loyarte y Enrique Loedel Palumbo, y analizamos sus trabajos pedagógicos más importantes y la recepción pública que tuvieron. Estos trabajos son una muestra del aporte del Instituto de Física a la elevación del nivel de educación nacional en el campo de las ciencias físicas en la primera mitad del siglo XX.(AU)

In the first decade of the 20th century, the Universidad Nacional de La Plata, founded in 1905, created a modern and well-equipped Physics Institute. In this paper we study the impact that this initiative had on the modernisation of physics teaching at secondary and university level in Argentina. We focus on two of the most representative graduates of the Institute in those years, Ramón G. Loyarte and Enrique Loedel Palumbo, and analyse their most important pedagogical works and the public reception they received. These works are a sample of the contribution of the Institute of Physics to the raising of the level of national education in the field of physical sciences in the first half of the 20th century.(AU)

Comparative assessment of water quality indices-a case study to evaluate water quality for drinking water supply and irrigation in Northern Mexico.

Water quality indices (WQIs) are numerical measures used by researchers and water managers to communicate water quality status to the public. This study analyzes the official databases from the CONAGUA monitoring network of the main tributary rivers in the middle basin of the San Pedro-Mezquital River in Durango, Mexico, for a 6-year period (2013-2018). We applied three WQIs to 432 data (18 sampling sites, four samples per year, 6 years): Canadian Council of Ministers of the Environment (CCME) WQI, National Sanitation Foundation (NSF) WQI, and Secretariat of Urban Development and Ecology (SEDUE) WQI. The Canadian index proved to be a flexible, appropriate, and rigorous methodology for assessing water quality based on its use. Results classify the water quality in the studied reservoirs as good, while river water was rated for public use, as marginal to very poor. No statistical significant differences in the quality of water between the rainy (June-October) and dry (November-May) seasons were found. However, tendency shows that in the rainy season the water quality was lower, mainly attributed to agricultural runoffs and bank erosion. The main contamination problem was the presence of fecal coliforms in high concentrations, which is associated to the high population density in the area, low sanitation efficiency, and multiple non-point discharges.

New insights into the interactions of HPV-16 E6*I and E6*II with p53 isoforms and induction of apoptosis in cancer-derived cell lines.

An important characteristic of cancers associated with high-risk human papillomaviruses (HR-HPV) is the inability of p53 to activate apoptosis due to the effect of the oncoprotein E6. However, the effect of HPV-16 E6 splice variant isoforms (namely E6*I and E6*II), their interaction with the existing p53 isoforms, and their influence on apoptosis is unclear. Here, we report the outcome of ectopic expression of HPV-16 E6, E6*I, and E6*II on the relative levels of p53 and p53 isoforms Δ40p53 and Δ133p53 and their interactions with these proteins. Additionally, we evaluated the effect of ectopic expression of p53, Δ40p53, and Δ133p53 on apoptosis in a p53 null pulmonary cell line (H1299) co-transfected with E6 isoforms and p53+/+ cell lines with HR-HPV (SiHa and HeLa), transfected with p53 isoforms and treated with cisplatin, a conventional drug used to treat cervical cancer. Our results show that E6 and E6*II induced a significant decrease in p53, but only E6 triggered a Δ40p53 decrease and that E6*II interacts with p53 but not with Δ40p53 and Δ133p53. On the other hand, E6*I did not show any effect or interaction with the p53 isoforms. We found that apoptosis was elevated in H1299 cells transfected with p53 (p = 0.0001) and Δ40p53 (p = 0.0001). A weak apoptotic effect was observed when Δ133p53 was ectopically expressed (p = 0.0195). We observed that both p53 (p = 0.0006) and Δ40p53 (p = 0.0014) induced apoptosis in cisplatin-treated SiHa cells; however in cisplatin-treated HeLa cells, only p53 induced apoptosis (p = 0.0029). No significant differences in apoptosis were observed upon ectopic expression of p53, Δ40p53, and Δ133p53 in SiHa and HeLa cells. Our findings suggest a possible therapeutic application for the combining of p53 or Δ40p53 with cisplatin to induce an increased apoptosis of cancer cells expressing E6 isoforms from HPV-16.

Biosimilar Versus Originator Pegfilgrastim for Preventing Chemotherapy-Induced Neutropenia: A Phase III Randomized, Multicenter, Evaluator-Blinded, Noninferiority Study.

PURPOSE: This study evaluated the efficacy, safety, and immunogenicity of biosimilar pegfilgrastim (PegFilBS) and originator pegfilgrastim (PegFilOR) in patients with stage 2-4 breast cancer. METHODS: This phase III randomized, multicenter, evaluator-blinded, noninferiority study recruited women with stage 2-4 breast cancer in Argentina who were scheduled to receive chemotherapy. Stratification was based on the breast cancer stage. The primary end point was the duration of severe neutropenia (DSN, noninferiority margin: 1 day) in the first chemotherapy cycle. Secondary end points assessed were incidence of severe neutropenia, grade 3 neutropenia, febrile neutropenia, infections, postchemotherapy hospitalization and duration, and the incidence of adverse drug reactions (ADRs). RESULTS: A total of 120 patients were randomly assigned to receive PegFilBS (58 patients) or PegFilOR (62 patients). Severe neutropenia occurred in 52 of 283 cycles (18.4%) for 27 patients who received PegFilBS and in 48 of 297 cycles (16.2%) for 20 patients who received PegFilOR (P = .48). During the first cycle, severe neutropenia occurred in 16 patients who received PegFilBS (DSN: 0.78 ± 1.53 days) and in 11 patients who received PegFilOR (DSN: 0.53 ± 1.25 days; 95% CI, -0.26 to 0.76 days). In the intention-to-treat analysis, the mean DSN values were 0.90 ± 1.79 days for the PegFilBS group and 0.50 ± 1.21 for the PegFilOR group (95% CI, -0.15 to 0.95 days). No significant differences were observed for the secondary efficacy end points. Three patients experienced seven ADRs in the PegFilBS group while 10 patients experienced 31 ADRs in the PegFilOR group. The most common ADR was myalgia. CONCLUSION: Relative to PegFilOR, PegFilBS provided noninferior efficacy outcomes in Argentinian women with stage 2-4 breast cancer who were treated using myelosuppressive chemotherapy.

SARS-CoV-2 Variants and Clinical Outcomes: A Systematic Review.

BACKGROUND: From the start of the COVID-19 pandemic, new SARS-CoV-2 variants have emerged that potentially affect transmissibility, severity, and immune evasion in infected individuals. In the present systematic review, the impact of different SARS-CoV-2 variants on clinical outcomes is analyzed. METHODS: A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020. Two databases (PubMed and ScienceDirect) were searched for original articles published from 1 January 2020 to 23 November 2021. The articles that met the selection criteria were appraised according to the Newcastle-Ottawa Quality Assessment Scale. RESULTS: Thirty-three articles were included, involving a total of 253,209 patients and 188,944 partial or complete SARS-CoV-2 sequences. The most reported SARS-CoV-2 variants showed changes in the spike protein, N protein, RdRp and NSP3. In 28 scenarios, SARS-CoV-2 variants were found to be associated with a mild to severe or even fatal clinical outcome, 15 articles reported such association to be statistically significant. Adjustments in eight of them were made for age, sex and other covariates. CONCLUSIONS: SARS-CoV-2 variants can potentially have an impact on clinical outcomes; future studies focused on this topic should consider several covariates that influence the clinical course of the disease.

Characteristics and growth of the genetic HIV transmission network of Mexico City during 2020.

INTRODUCTION: Molecular surveillance systems could provide public health benefits to focus strategies to improve the HIV care continuum. Here, we infer the HIV genetic network of Mexico City in 2020, and identify actively growing clusters that could represent relevant targets for intervention. METHODS: All new diagnoses, referrals from other institutions, as well as persons returning to care, enrolling at the largest HIV clinic in Mexico City were invited to participate in the study. The network was inferred from HIV pol sequences, using pairwise genetic distance methods, with a locally hosted, secure version of the HIV-TRACE tool: Seguro HIV-TRACE. Socio-demographic, clinical and behavioural metadata were overlaid across the network to design focused prevention interventions. RESULTS: A total of 3168 HIV sequences from unique individuals were included. One thousand and one-hundred and fifty (36%) sequences formed 1361 links within 386 transmission clusters in the network. Cluster size varied from 2 to 14 (63% were dyads). After adjustment for covariates, lower age (adjusted odds ratio [aOR]: 0.37, p<0.001; >34 vs. <24 years), being a man who has sex with men (MSM) (aOR: 2.47, p = 0.004; MSM vs. cisgender women), having higher viral load (aOR: 1.28, p<0.001) and higher CD4+ T cell count (aOR: 1.80, p<0.001; ≥500 vs. <200 cells/mm3 ) remained associated with higher odds of clustering. Compared to MSM, cisgender women and heterosexual men had significantly lower education (none or any elementary: 59.1% and 54.2% vs. 16.6%, p<0.001) and socio-economic status (low income: 36.4% and 29.0% vs. 18.6%, p = 0.03) than MSM. We identified 10 (2.6%) clusters with constant growth, for prioritized intervention, that included intersecting sexual risk groups, highly connected nodes and bridge nodes between possible sub-clusters with high growth potential. CONCLUSIONS: HIV transmission in Mexico City is strongly driven by young MSM with higher education level and recent infection. Nevertheless, leveraging network inference, we identified actively growing clusters that could be prioritized for focused intervention with demographic and risk characteristics that do not necessarily reflect the ones observed in the overall clustering population. Further studies evaluating different models to predict growing clusters are warranted. Focused interventions will have to consider structural and risk disparities between the MSM and the heterosexual populations.

The cross talk between gastric cancer stem cells and the immune microenvironment: a tumor-promoting factor.

Cross talk between cancer cells and the immune system is determinant for cancer progression. Emerging evidence demonstrates that GC characteristics such as metastasis, treatment resistance, and disease recurrence are associated with a tumor subpopulation called gastric cancer stem cells (GCSCs). However, the specific interaction between GCSCs and the immune microenvironment is still under investigation. Although immune evasion has been well described for cancer stem cells (CSCs), recent studies show that GCSCs can also regulate the immune system and even benefit from it. This review will provide an overview of bidirectional interactions between CSCs and immune cells in GC, compiling relevant data about how CSCs can induce leukocyte reprogramming, resulting in pro-tumoral immune cells that orchestrate promotion of metastasis, chemoresistance, tumorigenicity, and even increase in number of cancer cells with stem properties. Some immune cells studied are tumor-associated macrophages (TAMs), neutrophils, Th17 and T regulatory (Treg) cells, mesenchymal stem cells (MSCs), and cancer-associated fibroblasts (CAFs), as well as the signaling pathways involved in these pro-tumoral activities. Conversely, although there are cytotoxic leukocytes that can potentially eliminate GCSCs, we describe mechanisms for immune evasion in GCSCs and their clinical implications. Furthermore, we describe current available immunotherapy targeting GCSC-related markers as possible treatment for GC, discussing how the CSC-modified immune microenvironment can mitigate or inactivate these immunotherapies, limiting their effectiveness. Finally, we summarize key concepts and relevant evidence to understand the cross talk between GCSCs and the immune microenvironment as an important process for effective design of therapies against GCSCs that improve the outcome of patients with GC.

SARS-CoV-2 Reinfection among Healthcare Workers in Mexico: Case Report and Literature Review.

Since the onset of the COVID-19 pandemic, there have been multiple questions regarding reinfections associated with SARS-CoV-2. Healthcare workers on duty, due to overexposure in environments where there are more cases of COVID-19, are more prone to become infected by this virus. Here, we report 4 cases that meet the definition of clinical reinfection by SARS-CoV-2, as well as a literature review on this subject; all occurred in healthcare workers in Acapulco Guerrero, Mexico who provide their services in a hospital that cares for patients with COVID-19. The time between the manifestation of the first and second infection for each case was 134, 129, 107 and 82 days, all patients presented symptomatology in both events. The time between remission of the first infection and onset of second infection was 108, 109, 78 and 67 days for each case, while the time to confirmation by reverse transcription polymerase chain reaction (RT-PCR) between infections was 134, 124, 106 and 77 days. In two of the four cases the reinfection resulted in a more severe case, while in the remaining two cases the manifestation of symptoms and complications was similar to that presented in the first infection. Given this scenario, greater care is needed in the management of the pandemic caused by SARS-CoV-2 to protect healthcare workers and the general public from risks and complications caused by a possible reinfection by SARS-CoV-2.

Assessing tumor response to neoadjuvant chemoradiation in rectal cancer with rectoscopy and 18F-FDG PET/CT: results from a prospective series.

INTRODUCTION: rectoscopy and 18F-FDG PET/CT as a diagnostic algorithm for the assessment of tumor response in rectal cancer after neoadjuvant chemoradiation therapy (CRT) is very useful. MATERIAL AND METHODS: this was a prospective longitudinal study in patients with locally advanced rectal cancer treated with neoadjuvant CRT. Patients were assessed after CRT completion with a digital rectal examination, proctoscopy and 18F-FDG PET/CT. Patients were subdivided as clinical (cCR) or radiologic (rCR) responders and non-responders according to tumor response. Clinical and radiological re-assessment was compared with the surgical specimen. Pathological tumor regression (pCR) grade was determined according to Mandard's classification. Of the 68 patients included, 15 (22 %) presented pCR in the surgical specimen and tumor persistence (non-PCR) was detected in the remaining 53 (78 %). Clinical assessment (DRE+ rectoscopy) identified 15 patients as cCR and 53 as non-cCR, two were false positives and two were false negatives. The overall accuracy was 94 %. 18F-FDG PET/CT identified 18 patients as rCR and 50 as non-rCR, one was a false positive and four were false negatives. The overall accuracy was 92 %. A combination of clinical findings and 18F-FDG PET/CT resulted in an accuracy of 96 %. The combination of clinical findings + 18F-FDG PET/CT was able to correctly identify all cases of pCR, with the exception of one case that presented a tumor regression of 80 %. In this series, 18F-PET-CT and clinical assessment had excellent accuracies in differentiating PCR from non-PCR after CRT completion. PET-CT combined with clinical assessment had a better accuracy than both modalities independently. 18F-FDG PET/CT is a valid tool that complements the clinical assessment of tumor response.