Findings in Child Development in Children Who Grew Up During the COVID-19 Pandemic in Two Countries.

The COVID-19 pandemic created an unprecedented situation for families worldwide, with its potential impact on child development remaining uncertain, particularly within Latin American communities. This study aimed to analyze child development in children from Costa Rica and Mexico who grew up during COVID-19 pandemic. A cross-sectional study was conducted using a convenience sample of 183 children; a historical control group of Costa Rican children (n = 171) was also included.

Small bowel obstruction secondary to metastatic urothelial bladder cancer.

Small bowel obstruction secondary to primary cancer, such as carcinoid and adenocarcinoma, is not unusual. Less frequently, hematological metastasis from breast, lung, and melanoma can occur. However, metastasis from urothelial bladder carcinoma is extremely rare.

Factors Associated With Hip Fracture Length of Stay Among Older Adults in a Community Hospital Setting.

Introduction: Hip fractures in geriatric populations constitute a heavy burden on the healthcare system. The study goal was to identify patient, hospital, and surgical factors associated with hospital length of stay (LOS) for geriatric patients with hip fractures requiring surgical intervention in a community hospital setting.

Methods: This was a cross-sectional retrospective chart review of geriatric hip fractures that underwent surgical fixation at a community hospital between 2017 and 2019.

Abrocitinib for the Treatment of Moderate-to-Severe Atopic Dermatitis.

Background: Atopic dermatitis (AD) is ranked as the third most prevalent skin condition with a worldwide prevalence of 2.4%. Atopic dermatitis is a common form of eczema.

Amyloid-beta peptide and tau protein crosstalk in Alzheimer's disease.

Alzheimer's disease is a neurodegenerative disease that accounts for most of the 50-million dementia cases worldwide in 2018. A large amount of evidence supports the amyloid cascade hypothesis, which states that amyloid-beta accumulation triggers tau hyperphosphorylation and aggregation in form of neurofibrillary tangles, and these aggregates lead to inflammation, synaptic impairment, neuronal loss, and thus to cognitive decline and behavioral abnormalities. The poor correlation found between cognitive decline and amyloid plaques, have led the scientific community to question whether amyloid-beta accumulation is actually triggering neurodegeneration in Alzheimer's disease.

DNA methylation profiling identifies two distinct subgroups in breast cancers with low hormone receptor expression, mainly associated with HER2 amplification status.

Background: Current clinical guidelines suggest that breast cancers with low hormone receptor expression (LowHR) in 1-10% of tumor cells should be regarded as hormone receptor positive. However, clinical data show that these patients have worse outcome compared to patients with hormone receptor expression above 10%. We performed DNA methylation profiling on 23 LowHR breast cancer specimens, including 13 samples with HER2 amplification and compared our results with a reference breast cancer cohort from The Cancer Genome Atlas to clarify the status for this infrequent but important patient subgroup.

Production of Therapeutic Single-Chain Variable Fragments (ScFv) in Pichia pastoris.

The interest in the use of monoclonal antibodies as therapeutic molecules has raised in the recent years. Due to their high affinity and specificity towards other biological molecules, antibodies are being widely used to treat a broad range of human diseases such as cancer, rheumatism, and cardiovascular diseases. Currently, the production of IgG-like antibodies is mainly obtained from stable or transient mammalian expression systems that allow proper folding and posttranslational modifications.

Therapy response and prognosis of patients with early breast cancer with low positivity for hormone receptors - An analysis of 2765 patients from neoadjuvant clinical trials.

Aim: To evaluate HER2-negative breast cancer (BC) with a low hormone receptor (HR) expression, with regard to pathological complete response (pCR) and survival, in comparison to triple-negative BC (TNBC) and strong HR-positive BC.

Methods: We compared negative [oestrogen (ER) and progesterone receptor (PR) <1%], low-positive (ER and/or PR 1-9%) and strong-positive (ER or PR 10-100%) HR-expression in neoadjuvant clinical trial cohorts (n = 2765) of BC patients. End-points were disease-free survival (DFS), distant-disease free survival (DDFS) and overall survival (OS).

Preference for and reinforcing efficacy of different types of attention in preschool children.

It is unknown whether and to what extent common types of attention delivered in early childhood environments are preferred by and function as reinforcers for young children. We assessed children's preference for commonly delivered types of attention across 31 preschool-aged participants (Experiment 1). Next, we conducted a reinforcer assessment (Experiment 2) and a progressive-ratio assessment (Experiment 3) to (a) validate the results of the preference assessment and (b) determine the relative reinforcing efficacy of each type of attention.

Endocytosis-Mediated Replenishment of Amino Acids Favors Cancer Cell Proliferation and Survival in Chromophobe Renal Cell Carcinoma.

Chromophobe renal cell carcinoma (chRCC) accounts for approximately 5% of all renal cancers and around 30% of chRCC cases have mutations in . chRCC is poorly supported by microvessels and has markably lower glucose uptake than clear cell RCC and papillary RCC. Currently, the metabolic status and mechanisms by which this tumor adapts to nutrient-poor microenvironments remain to be investigated.

Cognitive Impairment in the 3xTg-AD Mouse Model of Alzheimer's Disease is Affected by Aβ-ImmunoTherapy and Cognitive Stimulation.

Clinical symptoms of Alzheimer's Disease (AD) include behavioral alterations and cognitive impairment. These functional phenotypes early occur in triple-transgenic (3xTg-AD) mice. Specifically, behavioral alterations are first detected when mice are at around 2.

Both Amyloid-β Peptide and Tau Protein Are Affected by an Anti-Amyloid-β Antibody Fragment in Elderly 3xTg-AD Mice.

Alzheimer's disease (AD) is the most common dementia worldwide. According to the amyloid hypothesis, the early accumulation of the Aβ-peptide triggers tau phosphorylation, synaptic dysfunction, and eventually neuronal death leading to cognitive impairment, as well as behavioral and psychological symptoms of dementia. ScFv-h3D6 is a single-chain variable fragment that has already shown its ability to diminish the amyloid burden in 5-month-old 3xTg-AD mice.

B cells expressing authentic naive human VRC01-class BCRs can be recruited to germinal centers and affinity mature in multiple independent mouse models.

Animal models of human antigen-specific B cell receptors (BCRs) generally depend on "inferred germline" sequences, and thus their relationship to authentic naive human B cell BCR sequences and affinities is unclear. Here, BCR sequences from authentic naive human VRC01-class B cells from healthy human donors were selected for the generation of three BCR knockin mice. The BCRs span the physiological range of affinities found in humans, and use three different light chains (VK3-20, VK1-5, and VK1-33) found among subclasses of naive human VRC01-class B cells and HIV broadly neutralizing antibodies (bnAbs).

Decreased Mitochondrial DNA Content Drives OXPHOS Dysregulation in Chromophobe Renal Cell Carcinoma.

Chromophobe renal cell carcinoma (chRCC) and renal oncocytoma are closely related, rare kidney tumors. Mutations in complex I (CI)-encoding genes play an important role in dysfunction of the oxidative phosphorylation (OXPHOS) system in renal oncocytoma, but are less frequently observed in chRCC. As such, the relevance of OXPHOS status and role of CI mutations in chRCC remain unknown.

Feasibility of Patient Navigation and Impact on Adherence to Screening Colonoscopy in a Large Diverse Urban Population.

Introduction: Disparities observed in colorectal cancer (CRC) incidence and mortality among blacks and Hispanics compared with whites may be in part due to lower screening rates. The New York City (NYC) Department of Health and Mental Hygiene (DOHMH) has implemented a patient navigator (PN) program at NYC hospitals serving lower-income patients to promote high adherence by patients referred for screening colonoscopy. A prior study showed this PN program increased adherence at 3 public hospitals.

Risk of infection and disease progression in children exposed to tuberculosis at home, Colombia.

Aim: To assess the risk of tuberculosis (infection and disease) in children less than 15 years' old who are household contacts of pulmonary tuberculosis patients in three Colombian cities (Medellín, Cali, and Popayán).

Methods: A cohort of 1,040 children household contacts of 380 adults with smear-positive pulmonary tuberculosis was followed up for 24 months. Study period 2005-2009.

Progression of Alzheimer's disease and effect of scFv-h3D6 immunotherapy in the 3xTg-AD mouse model: An in vivo longitudinal study using Magnetic Resonance Imaging and Spectroscopy.

Alzheimer's disease (AD) is an incurable disease that affects most of the 47 million people estimated as living with dementia worldwide. The main histopathological hallmarks of AD are extracellular β-amyloid (Aβ) plaques and intracellular neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau protein. In recent years, Aβ-immunotherapy has been revealed as a potential tool in AD treatment.

Low-density lipoprotein aggregation is inhibited by apolipoprotein J-derived mimetic peptide D-[113-122]apoJ.

Mimetic peptides are promising therapeutic agents for atherosclerosis prevention. A 10-residue class G* peptide from apolipoprotein J (apoJ), namely, D-[113-122]apoJ, possesses anti-inflammatory and anti-atherogenic properties. This prompted us to determine its effect on the aggregation process of low-density lipoprotein (LDL) particles, an early event in the development of atherosclerosis.

Using Drosophila Models and Tools to Understand the Mechanisms of Novel Human Cancer Driver Gene Function.

The formation, overgrowth and metastasis of tumors comprise a complex series of cellular and molecular events resulting from the combined effects of a variety of aberrant signaling pathways, mutations, and epigenetic alterations. Modeling this complexity in vivo requires multiple genes to be manipulated simultaneously, which is technically challenging. Here, we analyze how Drosophila research can further contribute to identifying pathways and elucidating mechanisms underlying novel cancer driver (risk) genes associated with tumor growth and metastasis in humans.

Papillary Renal Cell Carcinomas Rewire Glutathione Metabolism and Are Deficient in Both Anabolic Glucose Synthesis and Oxidative Phosphorylation.

Papillary renal cell carcinoma (pRCC) is a malignant kidney cancer with a prevalence of 7-20% of all renal tumors. Proteome and metabolome profiles of 19 pRCC and patient-matched healthy kidney controls were used to elucidate the regulation of metabolic pathways and the underlying molecular mechanisms. Glutathione (GSH), a main reactive oxygen species (ROS) scavenger, was highly increased and can be regarded as a new hallmark in this malignancy.

Treatment with scFv-h3D6 Prevented Neuronal Loss and Improved Spatial Memory in Young 3xTg-AD Mice by Reducing the Intracellular Amyloid-β Burden.

The intracellular deposition of amyloid-β (Aβ) peptides has been described in the brains of both Alzheimer's disease (AD) patients and animal models. A correlation between the intracellular amyloid burden and neurodegeneration has recently been reported in a triple-transgenic AD (3xTg-AD) murine model. In the present study, we assessed the effect of scFv-h3D6, an anti-Aβ single-chain variable fragment (scFv) derived from the antibody bapineuzumab, on amyloid pathology in 5-month-old 3xTg-AD female mice, focusing on intracellular Aβ clearance, neuronal survival, and functional abilities.

Pharmacokinetic parameters and mechanism of action of an efficient anti-Aβ single chain antibody fragment.

The success of the targeting of amyloid-β (Aβ) oligomers through immunotherapy in Alzheimer's disease (AD) mouse models has not been translated into the clinics. The use of single-chain variable fragments (scFvs) has been proposed to prevent the potential severe effects of full-length mAbs by precluding crystallizable fraction-mediated microglia activation. The efficacy of scFv-h3D6, a bapineuzumab-derived anti-Aβ scFv, has been extensively proven.

Molecular basis for the protective effects of low-density lipoprotein receptor-related protein 1 (LRP1)-derived peptides against LDL aggregation.

Aggregated LDL is the first ligand reported to interact with the cluster II CR9 domain of low-density lipoprotein receptor-related protein 1 (LRP1). In particular, the C-terminal half of domain CR9, comprising the region Gly-Cys exclusively recognizes aggregated LDL and it is crucial for aggregated LDL binding. Our aim was to study the effect of the sequence Gly-Cys (named peptide LP3 and its retro-enantio version, named peptide DP3) on the structural characteristics of sphingomyelinase- (SMase) and phospholipase 2 (PLA)-modified LDL particles.