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.

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.

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.

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.

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.

Differences in factors associated with anemia in Haitian children from urban and rural areas.

BACKGROUND: In Haiti, differences in the prevalence of anemia between urban and rural areas have been observed. OBJECTIVE: To identify moderating factors that may help explain the difference in the prevalence of anemia in children from poor urban vs. rural areas of Haiti. METHODS: This cross-sectional study used secondary data from urban and rural school-based trials that assessed the effectiveness of a nutrition intervention. The study was registered at ClinicalTrials.gov as NCT02747524. A total of 300 rural- and 981 urban- children between 2.5-13 years of age were included in this analysis. Effect modification in a binary logistic generalized linear mixed model was conducted using sample weights in SPSS® version 26. Models were adjusted for age and income. School cluster was included as random effect. RESULTS: In rural areas, stunting was more prevalent in children with anemia vs. no anemia, (16.6%, and 6.3%, P = 0.008), respectively. Also, rural children with anemia lived with fewer adults vs. rural children with no anemia, ([Formula: see text] = 2.83±1.29, and 3.30±1.54, P = 0.005), respectively. In poor urban areas, helminth morbidities were more frequent in children with anemia vs. no anemia, (21.9% vs. 13.9, P = 0.011), respectively. In the combined sample, stunting, [AOR = 2.05; 95%CI (1.32-3.18)], age [AOR = 0.89; 95%CI (0.85-0.93)], and households with more adults [AOR = 0.77; 95%CI (0.67-0.87)] were associated with anemia. Effect modification by place of residence was observed in households with more adults (t = 3.83, P<0.001). No other nutritional, dietary, sanitation or morbidity factors or effect modifiers were observed. CONCLUSIONS: In this sample, factors associated with anemia differed in poor urban and rural children from Haiti including family structure and helminth morbidities. Stunting and lower age increased the odds of anemia in the combined sample. Family structure appears to have an important role in anemia, and further research understanding the influence of family structures in anemia is needed.

Pulmonary nodular amyloidosis. A rare cause of multiple pulmonary nodules / Amiloidosis nodular pulmonar, una causa infrecuente de nódulos pulmonares múltiples

No disponible

Zinc deficiency associated with anaemia among young children in rural Guatemala.

One in four children younger than age five in Guatemala experiences anaemia (haemoglobin <11.0 g/dl). This study characterized the factors and micronutrient deficiencies associated with anaemia in a baseline cross-sectional sample of 182 Guatemalan infants/toddlers and 207 preschoolers, using generalized linear mixed models. Associations between anaemia and maternal, child and household variables, and biomarkers (soluble transferrin receptor, ferritin, zinc, folate, vitamin B12, C-reactive protein, and α1-acid glycoprotein) were explored. Rates of anaemia were 56% among infants/toddlers and 12.1% among preschoolers. In children with anaemia, rates of iron deficiency (low ferritin based on inflammation status, and/or high soluble transferrin receptor, ≥1.97 mg/L) and zinc deficiency (serum zinc <65 µg/dl) were 81.1% and 53.7%, respectively. Folate deficiency (either plasma folate <3 ng/ml or erythrocyte folate <100 ng/ml) was 3.3%. Vitamin B12 deficiency (plasma vitamin B12 <148 pmol/L) was 7.5%. For infants and toddlers (<24 months), the odds ratio of anaemia was lower when higher number of adults lived in the household (OR = 0.69; 95% CI [0.53, 0.90]), and higher when children were zinc deficient (OR = 3.40; 95% CI [1.54, 7.47]). For preschoolers (36-60 months), the odds ratio of anaemia was lower for every additional month of age (OR = 0.90; 95% CI [0.81, 1.00]). Findings suggest that micronutrient deficiencies coexist in Guatemalan rural children, and zinc deficiency is associated with anaemia in children <24 months, highlighting the need of continued multidisciplinary interventions with multiple micronutrients. Further research examining how household composition, feeding practices, and accessibility to micronutrient supplements and to animal source foods is needed to incorporate strategies to improve the nutritional status of Guatemalan children.

Aceptabilidad de un atole fortificado con 21 micronutrientes e impacto en la salud y nutrición de niños menores de 6 años de edad en la ciudad de guatemala / Acceptability of a 21 micronutrient-fortified atole and its impact on health and nutrition in children under 6 years of age from guatemala city

Con el objetivo de reducir la desnutrición crónica de niños que asisten 6 jardines infantiles en la Ciudad de Guatemala, se utilizó una bebida a base de soya y maíz como vehículo para el aporte de 21 micronutrientes con niveles elevados de hierro (12mg) y zinc (9mg) y se ofreció a 747 niños entre los 6 meses y 6 años. Se realizó seguimiento antropométrico cada 3m, Hb cada 6m y se registró el número de episodios de enfermedad diarreica aguda e infección respiratoria aguda a lo largo de la intervención. Un ANOVA longitudinal de medidas repetidas demostró que la media de la Hb mejoró de manera significativa a los 6 y 12m de recibir la bebida fortificada (11,26, 11,64, y 11,89g/dL, respectivamente), p<0,01; la prevalencia de anemia disminuyó 44,2% después de 12m, p<0,01; la media del puntaje z de talla para la edad también mejoró, -1,25 (0m) y -1,07 (12m), p<0.01; la prevalencia de retardo del crecimiento disminuyó 25% a los 12m. Se observó una disminución significativa en la prevalencia de infección respiratoria aguda y no se observaron cambios en la prevalencia de diarrea. Un estudio de aceptabilidad demostró que los niños consumen más del 98% del producto. Los resultados sugieren que la intervención con el atole fortificado mejora el estado nutricional y de salud de los niños. El producto es aceptado por los niños y el personal de los jardines infantiles(AU)

With the aim to reduce chronic undernutrition in children that attended 6 Guatemala City daycare centers, a corn and soy-based beverage was used as a vehicle to provide 21 micronutrients and high concentrations of iron (12mg) and zinc (9 mg) and was provided to747 children aged 6 to 72 months. Children were followed for anthropometry every 3m, hemoglobin every 6m, and episodes of acute diarrhea and respiratory tract infections were registered throughout the intervention. A longitudinal Repeated Measures ANOVA demonstrated that mean hemoglobin significantly improved at 6 and 12m of receiving the beverage (11.26, 11.64, and 11.89g/dL, respectively), p<0.01; the prevalence of anemia decreased by 44.2% after 12m, p<0.01; mean height-for-age z score improved from -1.25 (0m) to -1.07 (12m), p<0.01; the prevalence of stunting decreased by 25% after 12m. A significant decrease in the prevalence of acute respiratory infection was observed. No changes were observed in the prevalence of diarrhea. Moreover, an acceptability study showed that children consumed more than 98% of the atole. These results suggest that this nutrition intervention with the fortified atole improves the health and nutritional status of children. The product is widely accepted by the children and staff at the nurseries(AU)

Antiepileptic drugs and pregnancy outcomes.

The treatment of epilepsy in women of reproductive age remains a clinical challenge. While most women with epilepsy (WWE) require anticonvulsant drugs for adequate control of their seizures, the teratogenicity associated with some antiepileptic drugs (AEDs) is a risk that needs to be carefully addressed. Antiepileptic medications are also used to treat an ever broadening range of medical conditions such as bipolar disorder, migraine prophylaxis, cancer, and neuropathic pain. Despite the fact that the majority of pregnancies of WWE who are receiving pharmacological treatment are normal, studies have demonstrated that the risk of having a pregnancy complicated by a major congenital malformation is doubled when comparing the risk of untreated pregnancies. Furthermore, when AEDs are used in polytherapy regimens, the risk is tripled, especially when valproic acid (VPA) is included. However, it should be noted that the risks are specific for each anticonvulsant drug. Some investigations have suggested that the risk of teratogenicity is increased in a dose-dependent manner. More recent studies have reported that in utero exposure to AEDs can have detrimental effects on the cognitive functions and language skills in later stages of life. In fact, the FDA just issued a safety announcement on the impact of VPA on cognition (Safety Announcement 6-30-2011). The purpose of this document is to review the most commonly used compounds in the treatment of WWE, and to provide information on the latest experimental and human epidemiological studies of the effects of AEDs in the exposed embryos.

Genetic basis of susceptibility to teratogen induced birth defects.

Birth defects remain the leading cause of infant death in US. The field of teratology has been focused on the causes and underlying mechanisms of birth defects for decades, yet our understanding of these critical issues remain unacceptably vague. Conclusions from years of animal and human studies made it clear that the vast majority of birth defects have multifactorial origins, with contributions from environmental and genetic factors. The environment comprises not only of the physical, biological, and chemical external environment surrounding the pregnant woman, but it also includes the internal environment of the woman's body that interact with the developing embryo in a complex fashion. The importance of maternal and embryonic genetic factors consisting of countless genetic variants/mutations that exist within every individual contribute to birth defect susceptibility is only now being more fully appreciated. This great complexity of the genome and its diversity within individuals and populations seems to be the principal reason why the same teratogenic exposure can induce severe malformation in one embryo, while fail to do so to other exposed embryos. As the interaction between genetic and environmental factors has long been recognized as the first "Principle of Teratology" by Wilson and Warkany [1965. Teratology: Principles and techniques. Chicago: University of Chicago Press], it is only recently that the appropriate investigative tools have been developed with which to fully investigate this fundamental principle. The introduction of high throughput technologies like whole genome sequencing or genome-wide association studies are promising to deliver an enormous amount of new data that will shed light on the genomic factors that contribute susceptibility to environmental teratogens. In this review, we attempt to summarize the epidemiological and experimental literature concerning birth defects whose phenotypic expression can be clearly related to the interactions between several select environmental factors and those genetic pathways in which they are most likely to have significant modifying effects. © 2011 Wiley-Liss, Inc.

Teratogenic effects of antiepileptic drugs.

Many antiepileptic drugs (AEDs) have therapeutic applications that extend beyond epilepsy to include neuropathic pain, migraine headaches and psychiatric disorders. The risk of some AEDs has been clearly established, but for newer drugs, small sample sizes and polytherapy exposures preclude a conclusive determination of their teratogenic potential. Most women with epilepsy will require AED therapy throughout their entire pregnancy to control seizures; the vast majority of pregnancies in women with epilepsy have positive outcomes. A conservative estimate suggests that AED monotherapy doubles, and polytherapy triples, the risk for major congenital malformations. Furthermore, while evidence is still accruing, recent investigations suggest that exposure to select AEDs results in altered cognitive function later in development. There is no evidence to suggest that additional folic acid supplementation ameliorates the increased risk of congenital malformations conferred by in utero AED exposure.

Linfoma primario no Hodgkin difuso de células grandes B de vagina / Primary non-Hodgkin’s lymphoma of the vagina, diffuse large B-cell type

Los linfomas y las leucemias en etapas avanzadas pueden infiltrar el útero y la vagina. Sin embargo, la localización primaria del tracto genital femenino de los tumores hematológicos es extremadamente infrecuente (1% de los extraganglionares). Se presenta un caso de un linfoma no Hodgkin difuso de células grandes B primario de vagina en estadio IE, de acuerdo con la clasificación de Ann Arbor. Tras el tratamiento quimioradioterápico se obtuvo la remisión completa y la paciente permanece libre de enfermedad 5 años después del diagnóstico (AU)

Advanced lymphoma and leukemia can infiltrate the uterus and vagina. However, primary lymphomas affecting the female reproductive system are extremely uncommon (representing 1% of non-nodal tumors). We present a case of primary non-Hodgkin’s lymphoma of the vagina, diffuse large B cell type, stage IE according to the Ann-Arbor staging system. Complete remission was obtained after treatment with chemotherapy and radiotherapy. Five years after diagnosis, the patient is disease free (AU)