Capitalizing on Hope: Questionable Marketing Approval and Pricing of a New ALS Drug.

Regulatory agencies must balance patient demands to access new treatments for fatal diseases with limited treatment options while ensuring drug safety and efficacy. However, questionable U.S. regulatory actions resulted in the early approval of AMX0035 to treat amyotrophic lateral sclerosis (ALS) by reconvening advisory commissions to obtain positive decisions and designating the drug as a new molecular entity. Data from one randomized clinical trial suggests minimal delays in disease progression and longer survivability, but debate remains about the lack of confirmatory evidence of effectiveness owing to study limitations. A patient's decision-making process details the experience of using the drug, including perspectives on access, cost, effectiveness, and adverse effects. In line with the "nichebuster" business model, the drugmaker, Amylyx Pharmaceuticals, is charging US$158,000/year/patient and thus forecast to turn a profit on a drug with debatable clinical effectiveness prior to completing a Phase 3 trial. Early marketing approval, despite community demands, is unnecessary and may have reduced access because of the end of a compassionate use program, and the high price tag results in restricted coverage and high out-of-pocket costs. Also, the drug's key ingredients are available as a generic and a supplement.

Efficacy and Safety of the Extreme Lateral Interbody Fusion (XLIF) Technique in Spine Surgery: Meta-Analysis of 1409 Patients.

(1) Objectives: The objective of this study was to quantify the exact clinical-radiological efficacy and safety of the extreme lateral interbody fusion (XLIF) technique in spinal surgery; (2) Methods: A meta-analysis was performed using PubMed, Embase, Scopus, and Cochrane Collaboration Library. Studies focusing on patients surgically treated with XLIF were included. The outcomes were as follows: visual analog scale (VAS) and Oswestry disability index (ODI), radiological outcomes, and adverse events. Cohort studies and case series were also included. Clinical outcomes were assessed at 12 months of age. Data were combined using Review Manager 5.4 and WebPlotDigitizer 13.1.4; (3) Results: Nineteen studies with a pool of 1409 patients were included in this meta-analysis. Leg pain VAS and back pain VAS significantly improved at 12 months (SMD 2.75, 95% CI 0.59-4.90; SMD 4.54, 95% CI 1.39-7.69). ODI showed significant improvement (MD 32.51, 95% CI 24.01-41.00) at 12 months. Disc height increased significantly (SMD -2.73, 95% CI -3.58 to -1.88). Lumbar lordosis and segmental lordosis were significantly corrected postoperatively (MD -2.44, 95% CI -3.45 to -1.43; MD -2.55, 95% CI -3.61 to -1.48). The fusion rates at 12 months ranged from 85.0% to 93.3%. The most frequent complications were transient neurological conditions (2.2%), hardware failure (1.9%), and transient pain (1.8%). The most frequent serious complications were nerve root injury (1.0%), gastrointestinal impairment (0.7%), and vertebral fractures (0.6%); (4) Conclusions: This is the first meta-analysis of the specific use of XLIF in spinal surgery. This study demonstrates that the XLIF technique in spine surgery is associated with good clinical and radiological results and a low complication rate.

Ten-Year Follow-up of Posterior Chamber Phakic Intraocular Lens with Central Port Design in patients with low- and normal-vault.

PURPOSE: To assess the clinical outcomes and postoperative complications of the Implantable Collamer Lens (ICL) with a central port throughout ten years of follow-up in patients with low- and normal-vault. SETTING: Fernández-Vega Ophthalmological Institute, Oviedo, Spain. DESIGN: Retrospective and comparative case series. METHODS: This study included eyes that underwent a V4c ICL implantation with ten years of follow-up. The eyes were divided into two groups according to the vault at one year postoperatively: Vault < 250 µm; and between 250 and 800 µm. Uncorrected (UDVA), corrected distance visual acuity (CDVA), intraocular pressure (IOP), endothelial cell density (ECD), vault, complications and secondary surgeries were analysed. RESULTS: 37 and 90 eyes were enrolled in the low- and normal-vault groups. No differences in UDVA, CDVA and refraction were found between groups at ten years of follow-up. No cases developed ICL-induced anterior subcapsular opacity over the follow-up. Two (5.4%) and eight eyes (8.9%) in the low- and normal-vault-groups required ICL exchange. One (2.8%) and two eyes (2.2%) in the low- and normal-low-vault groups required excimer laser to correct residual refractive error. The IOP remained stable throughout the 10-year follow-up. The loss in ECD from the preoperative at the 10-year postoperatively was 3.8% and 4.5% in the low- and normal-vault groups (P=0.4). No pigment dispersion glaucoma or other vision-threatening complications were reported. CONCLUSIONS: This study shows the good long-term outcomes of the V4c ICL, supporting that the central hole provides safety to the procedure and prevents the potential risk associated with the low vault.

Clinical and Aberrometric Outcomes of a New Implantable Collamer Lens for Myopia and Presbyopia Correction in Phakic Patients.

PURPOSE: To assess the clinical and aberrometric outcomes of a new Implantable Collamer Lens (EVO Viva ICL; STAAR Surgical) to correct moderate to high myopia and presbyopia. METHODS: The study included 80 eyes of 40 patients who had bilateral EVO Viva ICL implantation. Uncorrected (UDVA) and corrected (CDVA) distance visual acuities, refraction, presbyopic add power, binocular through-focus visual acuity, total ocular spherical aberration (SA), coma aberration, and root mean square of ocular higher order aberrations (RMS HOAs) (i-Trace Aberrometer; Tracey Technologies) for a 4.5-mm pupil size were evaluated. RESULTS: The mean binocular postoperative UDVA and CDVA were 0.09 ± 0.19 and 0.02 ± 0.03 logMAR, respectively. The postoperative spherical equivalent was -0.61 ± 0.54 diopters (D). The presbyopic add power reduced from +1.31 ± 0.74 D preoperatively to +0.44 ± 0.58 D after surgery (P < .0001). The mean visual acuity was 0.1 logMAR or better (20/25 or better) across the vergence range from +0.50 to -1.50 D, better than 0.2 logMAR (20/32 or better) up to the vergence of -2.00 D, and remained better than 0.3 logMAR (20/40 or better) up to the vergence of -2.50 D. The total ocular aberrations induced by EVO Viva ICL were -0.34 ± 0.09 µm of SA, 0.24 ± 0.18 µm of coma, and 0.26 ± 0.12 µm of RMS HOAs. CONCLUSIONS: The outcomes support that the new ICL might be a good alternative for myopia and presbyopia correction in patients aged between 45 and 55 years. Further studies are needed to evaluate the threshold lens misalignment from which the patient´s visual quality would be affected. [J Refract Surg. 2023;39(9):589-596.].

Parental Knowledge and Perceptions on Prevention of Sudden Unexpected Infant Death and Infant Care.

(1) Background: The study's purpose was to explore the knowledge, perceptions, and confidence of mothers about infant care to reduce the risk of sudden unexpected infant death. (2) Methods: A purposeful sampling method was used to recruit 15 first-time mothers from Georgia with infants under 1 year of age. The researchers utilized the Socio-ecological model to report the results. Participants also provided recommendations on how to improve infant care and reduce the risk of SUID. (3) Results: The confidence level of infant care among most participants was low but increased over time. Mothers' knowledge level about the prevention of SUID was high, but poor emotional health could hurt their parental abilities. Most participants recognized medical providers as the main source of reliable information. However, a lack of emotional and physical support was reported by mothers. (4) Conclusions: Results suggested that a more holistic approach to infant care is needed. The healthcare system and communities should provide more physical, social, and mental support to first-time mothers, a consolidated approach to care before and after birth, and easy access to services at all stages of the process to reduce the risk of SUID.

CartoCell, a high-content pipeline for 3D image analysis, unveils cell morphology patterns in epithelia.

Decades of research have not yet fully explained the mechanisms of epithelial self-organization and 3D packing. Single-cell analysis of large 3D epithelial libraries is crucial for understanding the assembly and function of whole tissues. Combining 3D epithelial imaging with advanced deep-learning segmentation methods is essential for enabling this high-content analysis. We introduce CartoCell, a deep-learning-based pipeline that uses small datasets to generate accurate labels for hundreds of whole 3D epithelial cysts. Our method detects the realistic morphology of epithelial cells and their contacts in the 3D structure of the tissue. CartoCell enables the quantification of geometric and packing features at the cellular level. Our single-cell cartography approach then maps the distribution of these features on 2D plots and 3D surface maps, revealing cell morphology patterns in epithelial cysts. Additionally, we show that CartoCell can be adapted to other types of epithelial tissues.

Actitudes hacia el aborto deseado en estudiantes de ciencias de la salud chilenos / Attitudes towards wanted abortion among Chilean health sciences students

Introducción: La interrupción del embarazo mediando principalmente la voluntad de la mujer, es decir, cuando una mujer desea abortar para terminar su embarazo por cualquier razón, es un procedimiento controversial. Las actitudes individuales de los profesionales de la salud hacia este procedimiento influirían sobre la aceptación o el rechazo de realizarlo y, por ende, afectarían su acceso en el sistema de salud. Objetivo: Relacionar actitudes hacia la interrupción del embarazo con características sociodemográficas y académicas de estudiantes chilenos de enfermería, medicina y obstetricia y puericultura. Método: Estudio cuantitativo con diseño observacional, transversal y descriptivo. Reclutamos estudiantes universitarios con un muestreo no probabilístico. Recolectamos datos mediante cuestionarios virtuales autoadministrados. Preguntamos por la intención de realizar o asistir un aborto médico o quirúrgico frente a 15 escenarios distintos y creamos un índice con estas respuestas. Calculamos estadísticas descriptivas básicas y creamos modelos de regresión lineal. Consideramos significancia estadística si p < 0,05. Resultados: Participaron 229, 306 y 233 estudiantes de enfermería, medicina y obstetricia y puericultura, respectivamente (en total, 768). En el modelo de regresión lineal múltiple, declararse cristiano (β = −0,248) y afirmar que la religión es muy o totalmente importante en la vida (β = −0,269) se asociaron más fuertemente y de manera inversa y significativa con el índice de intención de realizar o asistir un aborto médico o quirúrgico. Conclusiones: La religión es un factor que influiría decisivamente sobre las actitudes hacia la interrupción del embarazo. Los escenarios más positivamente valorados podrían explicarse considerando que las leyes reflejarían los valores predominantes de una sociedad.

Introduction: Termination of pregnancy mediated primarily by the womans will, i.e., when a woman wishes to have an abortion to terminate her pregnancy for any reason, is a controversial procedure. The individual attitudes of health professionals towards this procedure would affect the degree of acceptance or rejection of performing this procedure and, therefore, would affect its accessibility in the health system. Objective: To relate attitudes towards abortion with sociodemographic and academic characteristics of Chilean nursing, medicine and midwifery students. Method: Quantitative study with observational, cross-sectional and descriptive design. We recruited university students with non-probabilistic sampling. We collected data through self-administered virtual questionnaires. We asked about the intention to perform an abortion in 15 different scenarios and created an index with these responses. We calculated basic descriptive statistics and created linear regression models. We considered statistical significance if p < 0.05. Results: 229, 306 and 233 students from nursing, medicine and midwifery participated, respectively (total: 768). In the multiple linear regression model, declaring oneself a Christian (β = −0.248) and stating that religion is very or totally important in life (β = −0.269) were inversely and significantly associated with the index of intention to perform an abortion. Conclusions: Religion is a factor that would decisively influence attitudes toward termination of pregnancy. The more positively valued scenarios could be explained by considering that laws would reflect the predominant values of a society.

The Effects of Multiple Micronutrient Fortified Beverage and Responsive Caregiving Interventions on Early Childhood Development, Hemoglobin, and Ferritin among Infants in Rural Guatemala.

Undernutrition and a lack of learning opportunities can jeopardize long-term growth and development among infants in low- and middle-income countries. We conducted a 6-month 2 × 2 cluster-randomized trial to assess the effects of multiple micronutrient-fortified beverages and responsive caregiving interventions among infants 6-18 months in 72 community sectors in southwest Guatemala. We administered baseline and endline assessments of childhood development (Bayley Scales of Infant and Toddler Development) and socioemotional development (Brief Infant Toddler Socio-Emotional Assessment) and measured ferritin and hemoglobin on a subsample. The trial was analyzed using linear mixed models. At the baseline, the mean age (SD) was 13.0 (4.6) months, including 49% males, 32% who were stunted, 55% who were anemic, and 58% who were iron deficient. At the endline (n = 328/386, 85% retention), there was no synergistic effect on the fortified beverage and responsive caregiving intervention. Compared to the non-fortified beverage group, socioemotional development improved in the fortified beverage group. There were no intervention effects on other measures of child development, hemoglobin, or ferritin. In a setting with high rates of anemia and iron deficiency, a multiple micronutrient-fortified beverage improved infants' socioemotional development.

Genetic variation in a tepary bean (Phaseolus acutifolius A. Gray) diversity panel reveals loci associated with biotic stress resistance.

Tepary bean (Phaseolus acutifolius A. Gray), indigenous to the arid climates of northern Mexico and the Southwest United States, diverged from common bean (Phaseolus vulgaris L.), approximately 2 million years ago and exhibits a wide range of resistance to biotic stressors. The tepary genome is highly syntenic to the common bean genome providing a foundation for discovery and breeding of agronomic traits between these two crop species. Although a limited number of adaptive traits from tepary bean have been introgressed into common bean, hybridization barriers between these two species required the development of bridging lines to alleviate this barrier. Thus, to fully utilize the extant tepary bean germplasm as both a crop and as a donor of adaptive traits, we developed a diversity panel of 422 cultivated, weedy, and wild tepary bean accessions which were then genotyped and phenotyped to enable population genetic analyses and genome-wide association studies for their response to a range of biotic stressors. Population structure analyses of the panel revealed eight subpopulations and the differentiation of botanical varieties within P. acutifolius. Genome-wide association studies revealed loci and candidate genes underlying biotic stress resistance including quantitative trait loci for resistance to weevils, common bacterial blight, Fusarium wilt, and bean common mosaic necrosis virus that can be harnessed not only for tepary bean but also common bean improvement.

Characterization of folic acid, 5-methyltetrahydrofolate and synthetic folinic acid in the high-affinity folate transporters: impact on pregnancy and development.

Folates are B vitamins that are essential for several molecular, cellular, and biological processes, including nucleotide synthesis, methylation, and methionine cycling. The physiological impacts of these processes on health also extend to cell proliferation, folate deficiency anemia, and reduction of the risk of birth defects during pregnancy. The primary objective of this study was to characterize the binding affinities of different folate forms, folic acid (FA), 5-methyltetrahydrofolate (5MTHF), and folinic acid, to the folate receptors α and ß, and to the bovine milk folate binding protein. These three dietary forms of folate are found in enriched grains (FA), various fruits and leafy vegetables (folinic acid), and red blood cells (5MTHF). Methods: The half maximal inhibitory concentration values and binding curves of each of these folates for each receptor were determined. Results: Our results indicated that FA had the highest affinity for all folate receptors, followed by 5MTHF, and lastly, by folinic acid, examined by several orders of magnitudes. Conclusion: These data are expected to provide new insights into the therapeutic applications of the different forms of folate in a variety of diseases.

Evaluation of Matrix Metalloproteases by Artificial Intelligence Techniques in Negative Biopsies as New Diagnostic Strategy in Prostate Cancer.

Usually, after an abnormal level of serum prostate-specific antigen (PSA) or digital rectal exam, men undergo a prostate needle biopsy. However, the traditional sextant technique misses 15-46% of cancers. At present, there are problems regarding disease diagnosis/prognosis, especially in patients' classification, because the information to be handled is complex and challenging to process. Matrix metalloproteases (MMPs) have high expression by prostate cancer (PCa) compared with benign prostate tissues. To assess the possible contribution to the diagnosis of PCa, we evaluated the expression of several MMPs in prostate tissues before and after PCa diagnosis using machine learning, classifiers, and supervised algorithms. A retrospective study was conducted on 29 patients diagnosed with PCa with previous benign needle biopsies, 45 patients with benign prostatic hyperplasia (BHP), and 18 patients with high-grade prostatic intraepithelial neoplasia (HGPIN). An immunohistochemical study was performed on tissue samples from tumor and non-tumor areas using specific antibodies against MMP -2, 9, 11, and 13, and the tissue inhibitor of MMPs -3 (TIMP-3), and the protein expression by different cell types was analyzed to which several automatic learning techniques have been applied. Compared with BHP or HGPIN specimens, epithelial cells (ECs) and fibroblasts from benign prostate biopsies before the diagnosis of PCa showed a significantly higher expression of MMPs and TIMP-3. Machine learning techniques provide a differentiable classification between these patients, with greater than 95% accuracy, considering ECs, being slightly lower when considering fibroblasts. In addition, evolutionary changes were found in paired tissues from benign biopsy to prostatectomy specimens in the same patient. Thus, ECs from the tumor zone from prostatectomy showed higher expressions of MMPs and TIMP-3 compared to ECs of the corresponding zone from the benign biopsy. Similar differences were found for expressions of MMP-9 and TIMP-3, between fibroblasts from these zones. The classifiers have determined that patients with benign prostate biopsies before the diagnosis of PCa showed a high MMPs/TIMP-3 expression by ECs, so in the zone without future cancer development as in the zone with future tumor, compared with biopsy samples from patients with BPH or HGPIN. Expression of MMP -2, 9, 11, and 13, and TIMP-3 phenotypically define ECs associated with future tumor development. Also, the results suggest that MMPs/TIMPs expression in biopsy tissues may reflect evolutionary changes from prostate benign tissues to PCa. Thus, these findings in combination with other parameters might contribute to improving the suspicion of PCa diagnosis.

Effectiveness of lactation cookies on human milk production rates: a randomized controlled trial.

BACKGROUND: Expensive lactation cookies (LCs) are marketed as milk boosters; however, their effectiveness remains unknown. OBJECTIVES: The objective of this study was to evaluate the effectiveness of the 1-mo daily intake of LCs on changes in objective and subjective milk production and breastfeeding self-efficacy. METHODS: This is a 1-mo, randomized controlled trial among 18-45-y-old exclusively lactating parents of healthy, term, 2-mo-old infants living in the United States from March to December 2021. Participants (n = 176) were randomly assigned to eat daily 56.5 g of either LCs with "galactagogues" (oatmeal, brewer's yeast, flax seeds, and fenugreek) or conventional cookies containing similar weight, calories, and presentation but lacking galactagogues. The primary outcome was baseline-to-1-mo changes in human milk production rate (HMPR), measured with a validated milk expression protocol. Secondary outcomes included changes in perceived insufficient milk (PIM) and lactation self-efficacy scores. RESULTS: Among 176 randomly assigned participants (age: 31.3 ± 5.8 y; 71.0% self-identified as White, 15.3% Hispanic/Latin, 6.3% Black, and 4.0% Asian), 90 participants (51.1%) completed endline HMPR measures and 129 (73.3%) completed secondary outcomes. Imputed models showed a mean increase in HMPR of 5.8 ± 15.7 mL/h in control participants and 5.5 ± 17.6 mL/h in the LC participants after 1 mo of daily intake of the cookie. No significant differences were observed with adjusted linear mixed models on the multiply imputed data comparing baseline-to-endline changes in HMPR, PIM, or breastfeeding self-efficacy: mean (SE) difference-in-differences for HMPR, -0.33 (4.97), P = 0.948; PIM scores (range: 5-50), -0.52 (1.83), P = 0.775; and self-efficacy scores (range: 14-70), 0.31 (2.23), P = 0.888, respectively. CONCLUSIONS: This study found no evidence for the effect of consuming LCs on HMPR, PIM, or breastfeeding self-efficacy in exclusively breastfeeding parents with an overall adequate perceived milk supply. Recommendations to consume LCs for increasing objective or subjective milk supply may deliver false hope and unnecessary financial costs at a vulnerable time. TRIAL REGISTRATION NUMBER: This trial was registered at clinicaltrials.gov as NCT04805008.

The Fetal Growth Restriction at Term Managed by Angiogenic Factors Versus Feto-Maternal Doppler (GRAFD) Trial to Avoid Adverse Perinatal Outcomes: Protocol for a Multicenter, Open-Label, Randomized Controlled Trial.

BACKGROUND: Fetal smallness affects 10% of pregnancies. Small fetuses are at a higher risk of adverse outcomes. Their management using estimated fetal weight and feto-maternal Doppler has a high sensitivity for adverse outcomes; however, more than 60% of fetuses are electively delivered at 37 to 38 weeks. On the other hand, classification using angiogenic factors seems to have a lower false-positive rate. Here, we present a protocol for the Fetal Growth Restriction at Term Managed by Angiogenic Factors Versus Feto-Maternal Doppler (GRAFD) trial, which compares the use of angiogenic factors and Doppler to manage small fetuses at term. OBJECTIVE: The primary objective is to demonstrate that classification based on angiogenic factors is not inferior to estimated fetal weight and Doppler at detecting fetuses at risk of adverse perinatal outcomes. METHODS: This is a multicenter, open-label, randomized controlled trial conducted in 20 hospitals across Spain. A total of 1030 singleton pregnancies with an estimated fetal weight ≤10th percentile at 36+0 to 37+6 weeks+days will be recruited and randomly allocated to either the control or the intervention group. In the control group, standard Doppler-based management will be used. In the intervention group, cases with a soluble fms-like tyrosine kinase to placental growth factor ratio ≥38 will be classified as having fetal growth restriction; otherwise, they will be classified as being small for gestational age. In both arms, the fetal growth restriction group will be delivered at ≥37 weeks and the small for gestational age group at ≥40 weeks. We will assess differences between the groups by calculating the relative risk, the absolute difference between incidences, and their 95% CIs. RESULTS: Recruitment for this study started on September 28, 2020. The study results are expected to be published in peer-reviewed journals and disseminated at international conferences in early 2023. CONCLUSIONS: The angiogenic factor-based protocol may reduce the number of pregnancies classified as having fetal growth restriction without worsening perinatal outcomes. Moreover, reducing the number of unnecessary labor inductions would reduce costs and the risks derived from possible iatrogenic complications. Additionally, fewer inductions would lower the rate of early-term neonates, thus improving neonatal outcomes and potentially reducing long-term infant morbidities. TRIAL REGISTRATION: ClinicalTrials.gov NCT04502823; https://clinicaltrials.gov/ct2/show/NCT04502823. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/37452.

Uncommon Cause of Hemoptysis in a 15-Year-Old Boy.

CASE PRESENTATION: A 15-year-old boy presented with three acute episodes of self-limited hemoptysis. He was being followed by the pediatric pulmonology department for necrotizing pneumonia and a right upper lobe lung abscess with residual pneumatocele 5 years earlier. He had also experienced recurrent perianal abscesses and more than 15 acute suppurative otitis media throughout his life, even after myringotomy and transtympanic drainage; methicillin-sensitive Staphyloccocus aureus was found in a culture of otic exudate. He had no known allergies and was not taking any drugs. The patient's father had presented with more than 20 skin abscesses and was carrier of methicillin-resistant S aureus. After necrotizing pneumonia and along with his family history, the patient had undergone a neutrophil oxidative burst test excluding chronic granulomatous disease; immunoglobulin levels and lymphocyte populations were within normal range.

Unilateral Loss of Maxillary Molars in Young Mice Leads to Bilateral Condylar Adaptation and Degenerative Disease.

The adaptive response of the mandible and temporomandibular joint (TMJ) to altered occlusion in juvenile patients is presently unclear. To address this question, we established a mouse model in which all molars were extracted from the maxillary right quadrant in prepubertal, 3-week-old mice and analyzed morphological, tissue, cellular, and molecular changes in the mandible and condyle 3 weeks later. Unilateral loss of maxillary molars led to significant, robust, bilateral changes, primarily in condylar morphology, including anteroposterior narrowing of the condylar head and neck and increased convexity at the condylar surface, as determined by geometric morphometric analysis. Furthermore, both condyles in experimental mice exhibited a degenerative phenotype, which included decreased bone volume and increased mineral density near the condylar head surface compared to control mice. Changes in condylar morphology and mineralized tissue composition were associated with alterations in the cellular architecture of the mandibular condylar cartilage, including increased expression of markers for mature (Col2a1) and hypertrophic (Col10a1) chondrocytes, suggesting a shift toward differentiating chondrocytes. Our results show significant bilateral condylar morphological changes, alterations in tissue composition, cellular organization, and molecular expression, as well as degenerative disease, in response to the unilateral loss of teeth. Our study provides a relatively simple, tractable mouse tooth extraction system that will be of utility in uncovering the cellular and molecular mechanisms of condylar and mandibular adaptation in response to altered occlusion. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

A quantitative biophysical principle to explain the 3D cellular connectivity in curved epithelia.

Epithelial cell organization and the mechanical stability of tissues are closely related. In this context, it has been recently shown that packing optimization in bended or folded epithelia is achieved by an energy minimization mechanism that leads to a complex cellular shape: the "scutoid". Here, we focus on the relationship between this shape and the connectivity between cells. We use a combination of computational, experimental, and biophysical approaches to examine how energy drivers affect the three-dimensional (3D) packing of tubular epithelia. We propose an energy-based stochastic model that explains the 3D cellular connectivity. Then, we challenge it by experimentally reducing the cell adhesion. As a result, we observed an increment in the appearance of scutoids that correlated with a decrease in the energy barrier necessary to connect with new cells. We conclude that tubular epithelia satisfy a quantitative biophysical principle that links tissue geometry and energetics with the average cellular connectivity.

Children Receiving a Nutrition and High-Quality Early Childhood Education Intervention Are Associated with Greater Math and Fluid Intelligence Scores: The Guatemala City Municipal Nurseries.

Background: About 47% of children < 5 years of age are stunted in Guatemala. In this study, the investigators aimed to compare growth and cognitive outcomes between children in second grade that attended five Guatemala City Municipal Nurseries (GCMN) vs. same sex, grade, and age-matched children. Methods: A cross-sectional design nested in a retrospective cohort was implemented between 2015 and 2019. Children that attended the GCMN and matched controls completed a math test and validated receptive language and fluid intelligence tests. The primary caregivers completed a sociodemographic survey. General and generalized linear mixed effect models were used to compare children that attended the GCMN vs. controls. The models were adjusted by maternal education, sex, asset score, and other relevant covariates. Results: Children that attended the GCMN exhibited greater math and fluid intelligence scores relative to the controls in the adjusted models (ß = 6.48; 95% CI (2.35−10.61)) and (ß = 1.20; 95% CI (0.12−2.29)), respectively. Lower odds of stunting were significant for children who went to any early childcare institution (AOR = 0.28; 95% CI (0.09−0.89)). Conclusions: The importance of integrating nutrition and high-quality early childhood education interventions in cognitive and growth outcomes is highlighted in this study. The GCMN model may be a scalable model in similar low-resource settings.