Knockdown of double-stranded RNases (dsRNases) enhances oral RNA interference (RNAi) in the corn leafhopper, Dalbulus maidis.

The leafhopper Dalbulus maidis is a harmful pest that causes severe damage to corn crops. Conventional chemical pesticides have negative environmental impacts, emphasizing the need for alternative solutions. RNA interference (RNAi) is a more specific and environmentally friendly method for controlling pests and reducing the negative impacts of current pest management practices. Previous studies have shown that orally administered double-stranded RNA (dsRNA) is less effective than injection protocols in silencing genes. This study focuses on identifying and understanding the role of double-stranded ribonucleases (dsRNases) in limiting the efficiency of oral RNAi in D. maidis. Three dsRNases were identified and characterized, with Dmai-dsRNase-2 being highly expressed in the midgut and salivary glands. An ex vivo degradation assay revealed significant nuclease activity, resulting in high instability of dsRNA when exposed to tissue homogenates. Silencing Dmai-dsRNase-2 improved the insects' response to the dsRNA targeting the gene of interest, providing evidence of dsRNases involvement in oral RNAi efficiency. Therefore, administering both dsRNase-specific and target gene-specific-dsRNAs simultaneously is a promising approach to increase the efficiency of oral RNAi and should be considered in future control strategies.

Clinical course of coronavirus disease-2019 in pregnancy.

INTRODUCTION: The aim of this study is to report our clinical experience in the management of pregnant women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the first 30 days of the coronavirus disease (COVID-19) pandemic. MATERIAL AND METHODS: We reviewed clinical data from the first 60 pregnant women with COVID-19 whose care was managed at Puerta de Hierro University Hospital, Madrid, Spain from 14 March to 14 April 2020. Demographic data, clinical findings, laboratory test results, imaging findings, treatment received, and outcomes were collected. An analysis of variance (Kruskal-Wallis test) was performed to compare the medians of laboratory parameters. Fisher's exact test was used to evaluate categorical variables. A correspondence analysis was used to explore associations between variables. RESULTS: A total of 60 pregnant women were diagnosed with COVID-19. The most common symptoms were fever and cough (75.5% each) followed by dyspnea (37.8%). Forty-one women (68.6%) required hospital admission (18 because of disease worsening and 23 for delivery) of whom 21 women (35%) underwent pharmacological treatment, including hydroxychloroquine, antivirals, antibiotics, and tocilizumab. No renal or cardiac failures or maternal deaths were reported. Lymphopenia (50%), thrombocytopenia (25%), and elevated C-reactive protein (CRP) (59%) were observed in the early stages of the disease. Median CRP, D-dimer, and the neutrophil/lymphocyte ratio were elevated. High CRP and D-dimer levels were the parameters most frequently associated with severe pneumonia. The neutrophil/lymphocyte ratio was found to be the most sensitive marker for disease improvement (relative risk 6.65; 95% CI 4.1-5.9). During the study period, 18 of the women (78%) delivered vaginally. All newborns tested negative for SARS-CoV-2 and none of them were infected during breastfeeding. No SARS-CoV-2 was detected in placental tissue. CONCLUSIONS: Most of the pregnant women with COVID-19 had a favorable clinical course. However, one-third of them developed pneumonia, of whom 5% presented a critical clinical status. CRP and D-dimer levels positively correlated with severe pneumonia and the neutrophil/lymphocyte ratio decreased as the patients improved clinically. Seventy-eight percent of the women had a vaginal delivery. No vertical or horizontal transmissions were diagnosed in the neonates during labor or breastfeeding.

Improvement in treatment abandonment in pediatric patients with cancer in Guatemala.

BACKGROUND: Treatment refusal and abandonment are major causes of treatment failure for children with cancer in low- and middle-income countries (LMICs), like Guatemala. This study identified risk factors for and described the intervention that decreased abandonment. METHODS: This was a retrospective study of Guatemalan children (0-18 years) with cancer treated at the Unidad Nacional de Oncología Pediátrica (UNOP), 2001-2008, using the Pediatric Oncology Network Database. Treatment refusal was a failure to begin treatment and treatment abandonment was a lapse of 4 weeks or longer in treatment. The impact of medicina integral, a multidisciplinary psychosocial intervention team at UNOP was evaluated. Cox proportional hazards analysis identified the effect of demographic and clinical factors on abandonment. Kaplan-Meier analysis estimated the survival. RESULTS: Of 1,789 patients, 21% refused or abandoned treatment. Abandonment decreased from 27% in 2001 to 7% in 2008 following the implementation of medicina integral. Factors associated with increased risk of refusal and abandonment: greater distance to the centre (P < 0.001), younger age (P = 0.017) and earlier year of diagnosis (P < 0.001). Indigenous race/ethnicity (P = 0.002) was associated with increased risk of abandonment alone. Abandonment correlated with decreased overall survival: 0.57 ± 0.02 (survival ± standard error) for those who completed therapy versus 0.06 ± 0.02 for those who abandoned treatment (P < 0.001) at 8.3 years. CONCLUSION: This study identified distance, age, year of diagnosis and indigenous race/ethnicity as risk factors for abandonment. A multidisciplinary intervention reduced abandonment and can be replicated in other LMICs.

Role of atrial tissue remodeling on rotor dynamics: an in vitro study.

The objective of this article is to present an in vitro model of atrial cardiac tissue that could serve to study the mechanisms of remodeling related to atrial fibrillation (AF). We analyze the modification on gene expression and modifications on rotor dynamics following tissue remodeling. Atrial murine cells (HL-1 myocytes) were maintained in culture after the spontaneous initiation of AF and analyzed at two time points: 3.1 ± 1.3 and 9.7 ± 0.5 days after AF initiation. The degree of electrophysiological remodeling (i.e., relative gene expression of key ion channels) and structural inhomogeneity was compared between early and late cell culture times both in nonfibrillating and fibrillating cell cultures. In addition, the electrophysiological characteristics of in vitro fibrillation [e.g., density of phase singularities (PS/cm(2)), dominant frequency, and rotor meandering] analyzed by means of optical mapping were compared with the degree of electrophysiological remodeling. Fibrillating cell cultures showed a differential ion channel gene expression associated with atrial tissue remodeling (i.e., decreased SCN5A, CACN1C, KCND3, and GJA1 and increased KCNJ2) not present in nonfibrillating cell cultures. Also, fibrillatory complexity was increased in late- vs. early stage cultures (1.12 ± 0.14 vs. 0.43 ± 0.19 PS/cm(2), P < 0.01), which was associated with changes in the electrical reentrant patterns (i.e., decrease in rotor tip meandering and increase in wavefront curvature). HL-1 cells can reproduce AF features such as electrophysiological remodeling and an increased complexity of the electrophysiological behavior associated with the fibrillation time that resembles those occurring in patients with chronic AF.

Changes in quality of nonaged pasta filata Mexican cheese during refrigerated vacuum storage.

Six batches of Oaxaca cheese (a Mexican pasta filata cheese) from 3 dairy plants were sampled and vacuum-packaged at 8°C up to 24d. Counts of principal microbial groups, pH, levels of sugars, organic acids, lipolytic and proteolytic indices, and texture, color, and meltability values of cheeses were studied at d 1, 8, 16 and 24 of storage. A descriptive sensory analysis of selected taste, odor, and texture characteristics was also carried out. The main changes in the cheeses during the storage were decreases in pH, hardness, elasticity, and whiteness, and an increase in meltability. Neither lipolytic nor proteolytic activities were evident during the storage of cheeses. Storage time resulted in a gradual quality loss of unmelted cheeses. This loss of quality might be related to the decrease of hardness and the appearance off-flavors.

Stigma in Pediatric Cancer: An Exploratory Study of Osteosarcoma and Retinoblastoma in Guatemala, Jordan, and Zimbabwe.

PURPOSE: Stigma is an understudied barrier to health care acceptance in pediatric oncology. We sought to explore the stigma experience, including its impact on cancer treatment decision making, and identify strategies to mitigate stigma for patients with osteosarcoma and retinoblastoma in Guatemala, Jordan, and Zimbabwe. METHODS: Participants included caregivers, adolescent patients (age 12-19 years), and health care clinicians. A semistructured interview guide based on The Health Stigma and Discrimination Framework (HSDF) was adapted for use at each site. Interviews were conducted in English, Spanish, Arabic, or Shona, audio-recorded, translated, and transcribed. Thematic analysis focused on stigma practices, experiences, outcomes, drivers, mitigators, and interventions. RESULTS: We conducted 56 interviews (28 caregivers, 19 health care clinicians, nine patients; 20 in Guatemala, 21 in Jordan, 15 in Zimbabwe). Major themes were organized into categories used to adapt the HSDF to global pediatric cancer care. Themes were described similarly across all sites, ages, and diagnoses, with specific cultural nuances noted. Pediatric cancer stigma was depicted as an isolating and emotional experience beginning at diagnosis and including internalized and associative stigma. Stigma affected decision making and contributed to negative outcomes including delayed diagnosis, treatment abandonment, regret, and psychosocial fragility. Overcoming stigma led to positive outcomes including resilience, treatment adherence, pride, and advocacy. Identified stigma drivers and mitigators were linked to potential interventions. CONCLUSION: Participants describe a shared stigma experience that transcends geography, cultural context, age, and diagnosis. Stigma manifestations have the potential to impact medical decision making and affect long-term psychological outcomes. Stigma assessment tools and interventions aimed at stigma mitigation including educational initiatives and support groups specific to pediatric cancer should be the focus of future research.

p16INK4a deficiency promotes IL-4-induced polarization and inhibits proinflammatory signaling in macrophages.

The CDKN2A locus, which contains the tumor suppressor gene p16(INK4a), is associated with an increased risk of age-related inflammatory diseases, such as cardiovascular disease and type 2 diabetes, in which macrophages play a crucial role. Monocytes can polarize toward classically (CAMϕ) or alternatively (AAMϕ) activated macrophages. However, the molecular mechanisms underlying the acquisition of these phenotypes are not well defined. Here, we show that p16(INK4a) deficiency (p16(-/-)) modulates the macrophage phenotype. Transcriptome analysis revealed that p16(-/-) BM-derived macrophages (BMDMs) exhibit a phenotype resembling IL-4-induced macrophage polarization. In line with this observation, p16(-/-) BMDMs displayed a decreased response to classically polarizing IFNγ and LPS and an increased sensitivity to alternative polarization by IL-4. Furthermore, mice transplanted with p16(-/-) BM displayed higher hepatic AAMϕ marker expression levels on Schistosoma mansoni infection, an in vivo model of AAMϕ phenotype skewing. Surprisingly, p16(-/-) BMDMs did not display increased IL-4-induced STAT6 signaling, but decreased IFNγ-induced STAT1 and lipopolysaccharide (LPS)-induced IKKα,ß phosphorylation. This decrease correlated with decreased JAK2 phosphorylation and with higher levels of inhibitory acetylation of STAT1 and IKKα,ß. These findings identify p16(INK4a) as a modulator of macrophage activation and polarization via the JAK2-STAT1 pathway with possible roles in inflammatory diseases.

Understanding hope at diagnosis: A study among Guatemalan parents of children with cancer.

BACKGROUND: In high-income countries, hope facilitates parental coping and builds the clinical relationship between families of children with cancer and their clinicians. However, the manifestation of hope in low- and middle-income countries (LMICs) remains poorly understood. Our study explores Guatemalan parents' experiences with hope during the pediatric oncology diagnostic process and aims to identify discrete actions clinicians take to support hope. METHODS: This qualitative study utilized audio-recordings of the diagnostic process and an additional semi-structured interview for 20 families of children with cancer at Unidad Nacional de Oncología Pediátrica in Guatemala. Spanish audio-recordings were translated into English, transcribed, and coded using a priori and novel codes. Thematic content analysis using constant comparative methods explored parents' hopes and concerns. RESULTS: At diagnosis, Guatemalan parents expressed both hopes and concerns related to the entire cancer continuum. Throughout the diagnostic process, hope grew as concerns were alleviated. Clinicians supported hope by creating a supportive environment, providing information, affirming religious beliefs, and empowering parents. These strategies helped parents shift their focus from fear and uncertainty toward hope for their child's future. Parents expressed that establishing hope improved mood, promoted acceptance, and enabled them to care for themselves and their children. CONCLUSION: These results confirm the relevance of supporting hope in pediatric oncology settings in LMICs and suggest that culture informs hope-related needs. Supporting hope is critical across cultures and can be integrated into clinical conversation using the four processes identified by our results.

An interactive way of learning about cancer and healthy living in a multicultural setting (part one)?

Health education is essential not only for preventing illnesses but also for knowing how to act when disease comes. In countries where the education system is inefficient for most of the population and where health issues are often ignored or mistreated because of ignorance or well-intended but ineffective belief in nature's energy and magic, it is important that people have access to truthful information about health issues. Such access allows them to act adequate knowledge and also to learn ways to avoid illness by changing their daily habits into a "healthy way of living." Approaching the young population is a way to achieve this objective. The program described here considers the education of both majority (indigenous) and minority (non indigenous) populations. It approaches the communication of information in such a way that it involves the participants in the "making" of the education. The participants actively interact with didactic material that allows them to experience "hands on" the issues about cancer and healthy living. It is intended to have a profound impact on the participant, so that he/she will remember the "education" not only as information but also as an experience. The program includes specific material for the indigenous population, which is based on their idiosyncrasy (corn plants) so that they can more easily understand the concepts. In Guatemala, UNOP (Unidad Nacional de Oncologia Pediatrica) is the only institution that provides a quality integral service for the majority of the entire children-with-cancer population. UNOP and the Psychology Department are interested in the development and implementation of education programs such as this where the participant not only learns but also experiences information about this disease and its prevention.

Clinical Management of Chronic Pelvic Pain in Endometriosis Unresponsive to Conventional Therapy.

BACKGROUND: Although several treatments are currently available for chronic pelvic pain, 30-60% of patients do not respond to them. Therefore, these therapeutic options require a better understanding of the mechanisms underlying endometriosis-induced pain. This study focuses on pain management after failure of conventional therapy. METHODS: We reviewed clinical data from 46 patients with endometriosis and chronic pelvic pain unresponsive to conventional therapies at Puerta de Hierro University Hospital Madrid, Spain from 2018 to 2021. Demographic data, clinical and exploratory findings, treatment received, and outcomes were collected. RESULTS: Median age was 41.5 years, and median pain intensity was VAS: 7.8/10. Nociceptive pain and neuropathic pain were identified in 98% and 70% of patients, respectively. The most common symptom was abdominal pain (78.2%) followed by pain with sexual intercourse (65.2%), rectal pain (52.1%), and urologic pain (36.9%). A total of 43% of patients responded to treatment with neuromodulators. Combined therapies for myofascial pain syndrome, as well as treatment of visceral pain with inferior or superior hypogastric plexus blocks, proved to be very beneficial. S3 pulsed radiofrequency (PRF) plus inferior hypogastric plexus block or botulinum toxin enabled us to prolong response time by more than 3.5 months. CONCLUSION: Treatment of the unresponsive patient should be interdisciplinary. Depending on the history and exploratory findings, therapy should preferably be combined with neuromodulators, myofascial pain therapies, and S3 PRF plus inferior hypogastric plexus blockade.

Understanding the Female Physical Examination in Patients with Chronic Pelvic and Perineal Pain.

(1) Background: The objective was to compare the exploration of chronic pelvic pain syndrome (CPPS) patients in different locations and establish the role of physical examination in CPPS patients. (2) Methods: We reviewed clinical data from 107 female patients with CPPS unresponsive to conventional therapies at Puerta de Hierro University Hospital Madrid, Spain, from May 2018 to June 2022. Patients were classified into three groups: (a) pelvic pain; (b) anorectal pain; or (c) vulvar/perineal pain. (3) Results: Although the demographics of patients with CPPS were different, their physical examinations were strikingly similar. Our study observed a comorbidity rate of 36% and 79% of central sensitization of pain. Seventy-one percent of patients had vulvar allodynia/hyperalgesia. Pain on examination was identified in any pelvic floor muscle, in any pelvic girdle structure, and neuropathic pain in 98%, 96%, and 89%, respectively. Patients with vulvar and perineal pain were more different from the other groups; these patients were younger and had fewer comorbidities and less central sensitization, less anorectal pain, more pain during intercourse, and greater nulliparity (p = 0.022; p = 0.040; p = 0.048; p = 0.000; p = 0.006; p = 0.005). (4) Conclusions: The findings of this study are related to the understanding of the pathophysiology of CPPS. The physical examination confirms the central sensitization of female patients with CPPS, helps us to determine the therapeutic management of the patient, and can be considered as a prognostic factor of the disease.

Development of efficient RNAi methods in the corn leafhopper Dalbulus maidis, a promising application for pest control.

BACKGROUND: The corn leafhopper Dalbulus maidis is the main vector of important stunting pathogens that affect maize production. Currently, there are no effective methods available to manage this pest without adverse impact on the environment. In this context, genomic-based technologies such as RNA interference (RNAi) provide a more environmentally friendly pest control strategy. Therefore, we aimed to assess the application of RNAi in D. maidis and determine the function of a candidate gene related to insect reproduction and propagation. RESULTS: We have characterized the core RNAi genes and evaluated the functionality of the RNAi machinery. We assessed the potential of RNAi technology in D. maidis via injection or ingestion of double-stranded RNA (dsRNA) to adult females. We chose Bicaudal C (BicC) as a target gene due to its important role during insect oogenesis. Administration of dsRNABicC caused significant reductions in the transcript levels (fold changes up to 170 times) and ovipositions. Phenotypic analysis of the ovaries revealed alterations in oocyte development, providing additional confirmation for our results and supporting the idea that Dmai-BicC is a key player of D. maidis oogenesis. CONCLUSION: This is, to our knowledge, the first report of efficient RNAi in D. maidis. We believe our findings provide a starting point for future control strategies against one of the most important maize pests in the Americas. © 2022 Society of Chemical Industry.

Cancer treatment decision-making among parents of paediatric oncology patients in Guatemala: a mixed-methods study.

OBJECTIVES: To examine treatment decision-making priorities and experiences among parents of children with cancer in Guatemala. SETTING: This study was conducted at Guatemala's National Pediatric Cancer Center in Guatemala City. PARTICIPANTS: Spanish-speaking parents of paediatric patients (≤18 years of age) diagnosed with any form of cancer within the 8 weeks prior to study enrolment. The quantitative portion of this study included 100 parent participants; the qualitative component included 20 parents. Most participants were Catholic or Evangelical Spanish-speaking mothers. OUTCOMES: Priorities and experiences of cancer treatment decision-making including decision-making role and experienced regret. RESULTS: A range of paediatric ages and cancer diagnoses were included. Most Guatemalan parents surveyed (70%) made decisions about their child's cancer together and almost all (94%) without input from their community. Surveyed parents predominately preferred shared decision-making with their child's oncologist (76%), however 69% agreed it was best not to be provided with many options. Two-thirds of surveyed parents (65%) held their preferred role in decision-making, with fathers more likely to hold their preferred role than mothers (p=0.02). A small number of parents (11%) experienced heightened decisional regret, which did not correlate with socio-demographic characteristics or preferred decision-making role. Qualitative results supported quantitative findings, demonstrating a decision-making process that emphasised trust and honesty. CONCLUSIONS: Guatemalan parents preferred to make decisions with their medical team and appreciated providers who were honest and inclusive, but directive about decisions. This study reinforces the importance of the provider-parent relationship and encourages clinicians in all settings to ask about and honour each parent's desired role in decision-making.

The evolution of parents' beliefs about childhood cancer during diagnostic communication: a qualitative study in Guatemala.

INTRODUCTION: Fatalistic cancer beliefs may contribute to delayed diagnosis and poor outcomes, including treatment abandonment, for children with cancer. This study explored Guatemalan parents' cancer beliefs during initial paediatric cancer communication, and the sociocultural and contextual factors that influence these beliefs. METHODS: Twenty families of children with cancer were included in this study. We audio-recorded psychosocial conversations with psychologists and diagnostic conversations with oncologists, then conducted semi-structured interviews with parents to explore the evolution of their cancer beliefs. Audio-recordings were transcribed and translated from Spanish into English, with additional review in both languages by bilingual team members. All 60 transcripts were thematically analysed using a priori and novel codes. RESULTS: Guatemalan parents' beliefs evolve as they learn about cancer through various sources. Sources of information external to the cancer centre, including prior experiences with cancer, media exposure, community discussion and clinical encounters, contribute to pre-existing beliefs. Many parents' pre-existing cancer beliefs are fatalistic; some are influenced by Mayan spirituality. Sources internal to the cancer centre include psychologists and oncologists, other providers, other patients and families. Psychologists acknowledge pre-existing beliefs and deliver cancer education using verbal explanations and hand-drawings. Oncologists provide diagnostic information and outline treatment plans. Both support hope by providing a path toward cure. Parents' lived experience is a culmination of sources and simultaneously independent. Ultimately most parents arrive at an understanding of cancer that is consistent with an allopathic medical model and offers optimism about outcomes. CONCLUSION: An interdisciplinary communication process that includes cancer education, is attentive to pre-existing beliefs, and supports hope may encourage acceptance of the allopathic medical model and need for treatment. Providers in settings of all resource levels may be able to use these techniques to support cross-cultural cancer communication, reduce treatment abandonment and improve therapy adherence.

Inflammatory protein sPLA(2)-IIA abrogates TNFalpha-induced apoptosis in human astroglioma cells: Crucial role of ERK.

Brain injury induces the expression of well-known cytokines, such as tumor necrosis factor-alpha (TNFalpha), and other, which functions are less understood, as secreted phospholipase A(2) group IIA (sPLA(2)-IIA). Since in pathological processes, cytokines function coordinately in networks, to further explore the actions of sPLA(2)-IIA in tumorigenesis, we investigated the effect of sPLA(2)-IIA in the presence of TNFalpha in human 1321N1 astrocytoma cells. In these cells, TNFalpha activates the apoptotic programme that is accompanied of cytoskeleton changes; however, simultaneous treatment with sPLA(2)-IIA prevents TNFalpha-mediated apoptosis and reverses the modification of the markers associated to this response. In fact, the mitogenic activity elicited by the phospholipase alone is preserved. This inhibitory effect is not found in other TNFalpha-mediated responses, even a functional cooperation is observed on COX-2 protein induction. The cross-talk between TNFalpha and sPLA(2)-IIA is associated with ERK activity since its pharmacological inhibition attenuates both synergistic and inhibitory responses. We have also observed that upon sPLA(2)-IIA stimulation, endogenous ERK has the capacity to bind and phosphorylate sequences present within the cytoplasmic domain of TNFR1/CD120a. These findings thus indicate that sPLA(2)-IIA and TNFalpha transduction pathways interact to modulate inflammatory responses and provide additional insights about the capacity of sPLA(2)-IIA to promote apoptosis resistance in astrocytoma cells.

Inflammatory mediators and insulin resistance in obesity: role of nuclear receptor signaling in macrophages.

Visceral obesity is coupled to a general low-grade chronic inflammatory state characterized by macrophage activation and inflammatory cytokine production, leading to insulin resistance (IR). The balance between proinflammatory M1 and antiinflammatory M2 macrophage phenotypes within visceral adipose tissue appears to be crucially involved in the development of obesity-associated IR and consequent metabolic abnormalities. The ligand-dependent transcription factors peroxisome proliferator activated receptors (PPARs) have recently been implicated in the determination of the M1/M2 phenotype. Liver X receptors (LXRs), which form another subgroup of the nuclear receptor superfamily, are also important regulators of proinflammatory cytokine production in macrophages. Disregulation of macrophage-mediated inflammation by PPARs and LXRs therefore underlies the development of IR. This review summarizes the role of PPAR and LXR signaling in macrophages and current knowledge about the impact of these actions in the manifestation of IR and obesity comorbidities such as liver steatosis and diabetic osteopenia.

Breastfeeding mothers with COVID-19 infection: a case series.

BACKGROUND: The first reports of the Chinese experience in the management of newborns of mothers with SARS-CoV 2 infection did not recommend mother-baby contact or breastfeeding. At present, the most important International Societies, such as WHO and UNICEF, promote breastfeeding and mother-baby contact as long as adequate measures to control COVID-19 infection are followed. In cases where maternal general health conditions impede direct breastfeeding or in cases of separation between mother and baby, health organizations encourage and support expressing milk and safely providing it to the infants. METHODS: A series of 22 case studies of newborns to mothers with COVID-19 infection from March 14th to April 14th, 2020 was conducted. Mothers and newborns were followed for a median period of 1.8 consecutive months. RESULTS: Out of 22 mothers, 20 (90.9%) chose to breastfeed their babies during hospital admission. Timely initiation and skin to skin contact at delivery room was performed in 54.5 and 59.1%, respectively. Eighty two percent of newborns to mothers with COVID-19 were fed with breast milk after 1 month, decreasing to 77% at 1.8 months. Six of 22 (37.5%) mothers with COVID-19 required transitory complementary feeding until exclusive breastfeeding was achieved. During follow-up period, there were no major complications, and no neonates were infected during breastfeeding. CONCLUSIONS: Our experience shows that breastfeeding in newborns of mothers with COVID-19 is safe with the adequate infection control measures to avoid mother-baby contagion. Supplementing feeding with pasteurized donor human milk or infant formula may be effective, until exclusive breastfeeding is achieved.

Synthesis, physicochemical characterisation and biological activity of anandamide/ɛ-polycaprolactone nanoparticles obtained by electrospraying.

Drug encapsulation in nanocarriers such as polymeric nanoparticles (Nps) may help to overcome the limitations associated with cannabinoids. In this study, the authors' work aimed to highlight the use of electrospraying techniques for the development of carrier Nps of anandamide (AEA), an endocannabinoid with attractive pharmacological effects but underestimated due to its unfavourable physicochemical and pharmacokinetic properties added to its undesirable effects at the level of the central nervous system. The authors characterised physicochemically and evaluated in vitro biological activity of anandamide/ɛ-polycaprolactone nanoparticles (Nps-AEA/PCL) obtained by electrospraying in epithelial cells of the human proximal tubule (HK2), to prove the utility of this method and to validate the biological effect of Nps-AEA/PCL. They obtained particles from 100 to 900 nm of diameter with a predominance of 200-400 nm. Their zeta potential was -20 ± 1.86 mV. They demonstrated the stable encapsulation of AEA in Nps-AEA/PCL, as well as its dose-dependent capacity to induce the expression of iNOS and NO levels and to decrease the Na+/K+ ATPase activity in HK2 cells. Obtaining Nps-AEA/PCL by electrospraying would represent a promising methodology for a novel AEA pharmaceutical formulation development with optimal physicochemical properties, physical stability and biological activity on HK2 cells.

Secreted phospholipase A2-IIA modulates key regulators of proliferation on astrocytoma cells.

Human group IIA secreted phospholipase A(2) (sPLA(2)-IIA) has been characterized in numerous inflammatory and neoplastic conditions. sPLA(2)-IIA can either promote or inhibit cell growth depending on the cellular type and the specific injury. We have previously demonstrated that exogenous sPLA(2)-IIA, by engagement to a membrane structure, induces proliferation and activation of mitogen-activated protein kinases cascade in human astrocytoma cells. In this study, we used human astrocytoma 1321N1 cells to investigate the key molecules mediating sPLA(2)-IIA-induced cell proliferation. We found that sPLA(2)-IIA promoted reactive oxygen species (ROS) accumulation, which was abrogated in the presence of allopurinol and DPI, but not by rotenone, discarding mitochondria as a ROS source. In addition, sPLA(2)-IIA triggered Ras and Raf-1 activation, with kinetics that paralleled ERK phosphorylation, and co-immunoprecipitation assays indicated an association between Ras, Raf-1 and ERK. Additionally, Akt, p70 ribosomal protein S6 kinase, and S6 ribosomal protein were also phosphorylated upon sPLA(2)-IIA treatment, effect that was abrogated by N-acetylcysteine or LY294002 treatment indicating that ROS and phosphatidylinositol 3 kinase are upstream signaling regulators. As the inhibitors N-acetylcysteine, PD98059, LY294002 or rapamycin blocked sPLA(2)-IIA-induced proliferation without activation of the apoptotic program, we suggest that inhibition of these intracellular signal transduction elements may represent a mechanism of growth arrest. Our results reveal new potential targets for therapeutic intervention in neuroinflammatory disorders and brain cancer in particular.

Current Drug Nano-targeting Strategies for Improvement in the Diagnosis and Treatment of Prevalent Pathologies such as Cardiovascular and Renal Diseases.

BACKGROUND: The kidney and cardiovascular system are closely related to each other during the modulation of the cardiovascular homeostasis. However, the search for new alternatives for the treatment and diagnosis of cardiovascular diseases does not take into account this relationship, so their evaluation results and the advantages offered by their global and integrative analysis are wasted. For example, a variety of receptors that are overexpressed in both pathologies is large enough to allow expansion in the search for new molecular targets and ligands. Nanotechnology offers pharmacological targeting strategies to kidney, heart, and blood vessels for overcoming one of the essential restrictions of traditional cardiovascular therapies the ones related to their unspecific pharmacodynamics distribution in these critical organs. RECENT FINDINGS: Drug or contrast agent nano-targeting for treatment or diagnosis of atherosclerosis, thrombosis, renal cancer or fibrosis, glomerulonephritis, among other renal, cardiac and blood vessels pathologies would allow an increase in their efficacy and a reduction of their side effects. Such effects are possible because, through pharmacological targeting, the drug is mainly found at the desired site. Review Purpose: In this mini-review, active, passive, and physical targeting strategies of several nanocarriers that have been assessed and proposed for the treatment and diagnosis of different cardiovascular diseases, are being addressed.