CRISPR/Cas9 Eye Drop HSV-1 Treatment Reduces Brain Viral Load: A Novel Application to Prevent Neuronal Damage.

Herpes simplex virus-1 (HSV-1) can invade the central nervous system (CNS). However, antiviral drugs used to treat HSV-1 have significant toxicity and resistance. An alternative approach involves the use of the CRISPR/Cas9 complex as a viral replication inhibitor.

Real life data of ONC201 (dordaviprone) in pediatric and adult H3K27-altered recurrent diffuse midline glioma: Results of an international academia-driven compassionate use program.

Introduction: H3K27-altered diffuse midline gliomas (DMG) have limited therapeutic options and a very poor prognosis. Encouraging responses were observed in early clinical trials with ONC201. As ONC201 was unavailable in Europe, a compassionate use program supported by the French Authorities was launched for patients at progression after standard of care radiotherapy.

UHT Cow's Milk Supplementation Affects Cell Niches and Functions of the Gut-Brain Axis in BALB/c Mice.

Background/objectives: Cow's milk is a bioactive cocktail with essential nutritional factors that is widely consumed during early childhood development. However, it has been associated with allergic responses and immune cell activation. Here, we investigate whether cow's milk consumption regulates gut-brain axis functions and affects patterns of behaviors in BALB/c mice, previously described by present low sociability, significant stereotypes, and restricted interest features.

Short and long-term effects of kidney donation on mineral and bone metabolism.

Background: Living kidney donors (LKD) experience an abrupt decline in glomerular filtration rate (GFR) resulting in abnormalities of mineral and bone metabolism (MBD), and this may have implications for skeletal health. We prospectively studied acute and long term MBD adaptation of LKD from two kidney transplant centers (São Paulo, Brazil and Miami, USA).

Methods: Renal function and MBD parameters longitudinally after kidney donation (baseline - D0, day 1, 14, 180 and 360 post-operatively) were measured in 74 patients (40 y, 73% female, 54% Brazilian).

Effects of two immunosuppression regimens on T-lymphocyte subsets in elderly kidney transplant recipients.

Background: Despite the growing number of elderly kidney transplant (Ktx) recipients, few studies have examined the effects of immunosuppression on their lymphocyte profiles.

Methods: We evaluated the early conversion from mycophenolate sodium (MPS) to everolimus (EVL) after rabbit antithymocyte globulin (rATG) 2 mg/kg induction in elderly kidney recipients. Three groups of KTx patients were compared: (a) Young (n=20, 36 ± 7 y) receiving standard immunosuppression (Group A1) (prednisone, tacrolimus, and MPS), (b) Elderly (n=35, 65 ± 3 y) receiving standard immunosuppression (Group B1), and (c) Elderly (n=16, 65 ± 3 y) with early (mean 30 d) conversion from MPS to EVL (Group B2).

Live software documentation of design pattern instances.

Background: Approaches to documenting the software patterns of a system can support intentionally and manually documenting them or automatically extracting them from the source code. Some of the approaches that we review do not maintain proximity between code and documentation. Others do not update the documentation after the code is changed.

Tetrameric, active PKM2 inhibits IP receptors, potentially requiring GRP75 as an additional interaction partner.

Pyruvate kinase M2 (PKM2) is a key glycolytic enzyme interacting with the inositol 1,4,5-trisphosphate receptor (IPR). This interaction suppresses IPR-mediated cytosolic [Ca] rises. As PKM2 exists in monomeric, dimeric and tetrameric forms displaying different properties including catalytic activity, we investigated the molecular determinants of PKM2 enabling its interaction with IPRs.

Immunosuppression-induced Zika virus reactivation causes brain inflammation and behavioral deficits in mice.

Zika virus (ZIKV) is a neurotropic flavivirus that can persist in several tissues. The late consequences of ZIKV persistence and whether new rounds of active replication can occur, remain unaddressed. Here, we investigated whether neonatally ZIKV-infected mice are susceptible to viral reactivation in adulthood.

Depressive symptoms and oral mucositis in children with oncological diseases: a cross-sectional study.

The aim of this study was to investigate the correlation between depressive symptoms and the occurrence of oral mucositis in children with oncological diseases treated at a reference hospital. This was a cross-sectional study conducted with individuals aged 4 to 18 years, diagnosed with primary neoplasms. Data was collected by using a questionnaire that assessed the degree of oral mucositis according to the World Health Organization index, the risk of oral mucositis according to the Child's International Mucositis Evaluation Scale, and depressive symptoms using the Children's Depression Inventory.

Immune pathway through endometriosis to ovarian cancer.

Endometriosis is an estrogen-dependent inflammatory disease, defined by the presence of functional endometrial tissue outside of the uterine cavity. This disease is one of the main gynecological diseases, affecting around 10%-15% women and girls of reproductive age, being a common gynecologic disorder. Although endometriosis is a benign disease, it shares several characteristics with invasive cancer.

New avenues for the treatment of immunotherapy-resistant pancreatic cancer.

Pancreatic cancer (PC) is characterized by its extremely aggressive nature and ranks 14th in the number of new cancer cases worldwide. However, due to its complexity, it ranks 7th in the list of the most lethal cancers worldwide. The pathogenesis of PC involves several complex processes, including familial genetic factors associated with risk factors such as obesity, diabetes mellitus, chronic pancreatitis, and smoking.

Urea breath test for infection in adult dyspeptic patients: A meta-analysis of diagnostic test accuracy.

Background: () infection has been well-established as a significant risk factor for several gastrointestinal disorders. The urea breath test (UBT) has emerged as a leading non-invasive method for detecting . Despite numerous studies confirming its substantial accuracy, the reliability of UBT results is often compromised by inherent limitations.

Phylogeographic analyses of an endemic Neotropical fox (Lycalopex vetulus) reveal evidence of hybridization with a different canid species (L. gymnocercus).

The hoary fox (Lycalopex vetulus) is the only species of the Canidae (Mammalia: Carnivora) endemic to Brazil, and so far has been the target of few genetic studies. Using microsatellites and mtDNA markers, we investigated its present genetic diversity and population structure. We also tested the hypothesis that this species currently hybridizes with the pampas fox (L.

Topical capsaicin 8% patch in peripheral neuropathic pain: Efficacy and quality of life.

Introduction: Peripheral neuropathic pain (PNP) is one of the most challenging diseases to treat with a significant negative impact on the patients' health-related quality of life (HRQoL). Capsaicin 8% patch has arisen in the last decades as an alternative to oral drugs in the treatment of PNP with fewer side effects and promising results in efficacy.

Objectives: This work aims to evaluate the effectiveness of the topical application of capsaicin in PNP and its impact on patients' HRQoL based on the use of capsaicin in a tertiary hospital of Oporto.

The interplay between associated proteins, redox state and Ca in the intraluminal ER compartment regulates the IP receptor.

There have been in the last three decades repeated publications indicating that the inositol 1,4,5-trisphosphate receptor (IPR) is regulated not only by cytosolic Ca but also by intraluminal Ca. Although most studies indicated that a decreasing intraluminal Ca level led to an inhibition of the IPR, a number of publications reported exactly the opposite effect, i.e.

The Complex Effects of PKM2 and PKM2:IPR Disruption on Intracellular Ca Handling and Cellular Functions.

Pyruvate kinase M (PKM) 2 was described to interact with the inositol 1,4,5-trisphosphate (IP) receptor (IPR) and suppress its activity. To further investigate the physiological importance of the PKM2:IPR interaction, we developed and characterized HeLa PKM2 knockout (KO) cells. In the HeLa PKM2 KO cells, the release of Ca to the cytosol appears to be more sensitive to low agonist concentrations than in HeLa wild-type (WT) cells.

Role of non- gastric Helicobacters in -negative gastric mucosa-associated lymphoid tissue lymphoma.

Marginal zone lymphomas rank as the third most prevalent form of non-Hodgkin B-cell lymphoma, trailing behind diffuse large B-cell lymphoma and follicular lymphoma. Gastric mucosa-associated lymphoid tissue lymphoma (GML) is a low-grade B-cell neoplasia frequently correlated with ()-induced chronic gastritis. On the other hand, a specific subset of individuals diagnosed with GML does not exhibit infection.

Correction to "Performance of a serological IgM and IgG qualitative test for COVID-19 diagnosis: An experimental study in Brazil".

[This corrects the article on p. 100 in vol. 12, PMID: 36196438.

Pediatric multisystem inflammatory syndrome associated with COVID-19: Insights in pathogenesis and clinical management.

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been a major challenge to be faced in recent years. While adults suffered the highest morbidity and mortality rates of coronavirus disease 2019, children were thought to be exclusively asymptomatic or to present with mild conditions. However, around April 2020, there was an outbreak of a new clinical syndrome related to SARS-CoV-2 in children - multisystemic inflammatory syndrome in children (MIS-C) - which comprises a severe and uncon-trolled hyperinflammatory response with multiorgan involvement.

The ER-mitochondria interface, where Ca and cell death meet.

Endoplasmic reticulum (ER)-mitochondria contact sites are crucial to allow Ca flux between them and a plethora of proteins participate in tethering both organelles together. Inositol 1,4,5-trisphosphate receptors (IPRs) play a pivotal role at such contact sites, participating in both ER-mitochondria tethering and as Ca-transport system that delivers Ca from the ER towards mitochondria. At the ER-mitochondria contact sites, the IPRs function as a multi-protein complex linked to the voltage-dependent anion channel 1 (VDAC1) in the outer mitochondrial membrane, via the chaperone glucose-regulated protein 75 (GRP75).

Immunotherapy in glioblastoma treatment: Current state and future prospects.

Glioblastoma remains as the most common and aggressive malignant brain tumor, standing with a poor prognosis and treatment prospective. Despite the aggressive standard care, such as surgical resection and chemoradiation, median survival rates are low. In this regard, immunotherapeutic strategies aim to become more attractive for glioblastoma, considering its recent advances and approaches.

Effectiveness of eradication in the treatment of early-stage gastric mucosa-associated lymphoid tissue lymphoma: An up-to-date meta-analysis.

Background: Gastric mucosa-associated lymphoid tissue (MALT) lymphoma (GML) is usually a low-grade B-cell neoplasia strongly associated with ()-induced chronic gastritis. Clinical practice guidelines currently recommend eradication as the preferred initial treatment for early-stage GML. To determine the practical effect of bacterial eradication as the sole initial therapy for early-stage GML, an updated analysis and review of available evidence is imperative.