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The purpose of this article was to extend the model used to predict selection response with selfed progeny from 2 alleles per locus to a model which is general for number and frequency of alleles at loci. To accomplish this, 4 areas had to be dealt with: 1) simplification of the derivation and calculation of the condensed coefficients of identity; 2) presentation of the genetic variances expressed among and within selfed progenies as linear function of 5 population parameters; 3) presentation of selection response equations for selfed progenies as functions of these 5 population parameters; and 4) to identify a set of progeny to evaluate, such that one might be able to estimate these 5 population parameters. The five population parameters used in predicting gains were the additive genetic variance, the dominance variance, the covariance of additive and homozygous dominance deviations, the variance of the homozygous dominance deviations and a squared inbreeding depression term. [ABSTRACT FROM AUTHOR]

In this study we have examined serum from patients with Plasmodium falciparum malaria, collected at the time of acute attack and 14 days later. We have also examined sequential samples of sera taken from children living in Madang Province, Papua New Guinea, an area endemic for malaria. The total amount of antibody directed against P. falciparum in acute phase sera was less than that found in matched controls. An in vitro assay measuring inhibition of penetration of uninfected erythrocytes by merozoites of P. falciparum revealed less inhibitory activity in acute phase sera than in matched controls. The longitudinal study of sera from village children demonstrated that non-specific inhibition of intracellular parasite growth was fairly stable, while merozoite inhibiting activity was unstable and varied with time. A cloned P. falciparum species has been used to directly demonstrate the specific growth enhancement by serum in vitro. [ABSTRACT FROM AUTHOR]

The article presents a study that has modified a micro Plasmodium falciparum in vitro growth inhibition assay to allow dissection of growth inhibition. This was achieved using morphology-controlled synchronised cultures with incubation times restricted to cover either ring to schizont development or schizont to ring development. Sera tested were obtained from a large prospective study of healthy residents of Madang, Papua New Guinea, who were carefully documented with respect to presence of malarial parasites in the blood, spleen size, age, sex and history of fever.

Presents a study where Plasmodium falciparum malaria was cultured in vitro in the presence of sera from patients with cerebral malaria, meningitis and also after chloroquine administration. Discovery of the intra-erythrocytic parasite damage by light and electron microscopy; Discussion of the results with relevance to non-specific immune mechanisms; Comparison of the damage induced by the mechanisms with that from chloroquine.

Background: Health professionals are increasingly being called to address the social determinants of health (SDOH) and, to do so effectively, often requires an integrated approach to care. As a result, accreditation standards across multiple professions have emphasised the importance of interprofessional education (IPE)., Approach: This paper describes large-scale, community-engaged learning that is required annually of students from nursing, pharmacy, public health, and social work. Through a series of asynchronous and synchronous activities that are informed by the Interprofessional Education Collaborative core competencies, students are trained to be SDOH change makers who can readily adopt integrated care service delivery frameworks into their future practice., Evaluation: Approximately 1000 students have participated in this event since the University launched its IPE curriculum in 2017. Student consistently report achievement of the course learning objectives, with 91% of students reporting that the learning activities enhanced their understanding of their professional roles/responsibilities in regards to addressing poverty and food insecurity., Implications: Two key lessons learned from these efforts are described, including the benefits of a trauma-informed pedagogical approach and special considerations for large-scale learning., (© 2023 Association for the Study of Medical Education and John Wiley & Sons Ltd.)

Food fraud is an ever-present threat that regulators, food business operators (FBOs), and consumers need to be aware of, prevent where possible, and address by developing mitigation strategies to detect and reduce its negative consequences. While extant literature focuses on food fraud detection, there is less attention given to prevention strategies, a knowledge gap this review seeks to address. The aim of this review was to consider food-related fraud prevention initiatives, understand what has worked well, and develop a series of recommendations on preventing food fraud, both policy related and for future research. Reactive (including intelligence based) food fraud detection dominates over prevention strategies, especially where financial, knowledge, and time resources are scarce. First-generation tools have been developed for food fraud vulnerability assessment, risk analysis, and development of food fraud prevention strategies. However, examples of integrated food control management systems at FBO, supply chain, and regulatory levels for prevention are limited. The lack of hybrid (public/private) integration of food fraud prevention strategies, as well as an effective verification ecosystem, weakens existing food fraud prevention plans. While there are several emergent practice models for food fraud prevention, they need to be strengthened to focus more specifically on capable guardians and target hardening. This work has implications for policymakers, Official Controls bodies, the food industry, and ultimately consumers who seek to consistently purchase food that is safe, legal, and authentic., (© 2024 The Author(s). Comprehensive Reviews in Food Science and Food Safety published by Wiley Periodicals LLC on behalf of Institute of Food Technologists.)

Novel externalities are social activities for which the emerging cost (or benefit) of the spillover is unknown and must be discovered. Negative novel externalities have regained international salience following the COVID-19 pandemic. Such cases frequently are invoked as evidence of the limits of liberal political economy for dealing with public emergencies. Through a re-reading of classical political economy with the modern state's confrontation with infectious disease in mind, we defend the comparative efficacy of liberal democracy against authoritarian alternatives for coping with these social problems. Effective responses to novel externalities require producing and updating trustworthy public information and an independent scientific community to validate and interpret it. Those epistemic capacities are prevalent in liberal democratic regimes with multiple sources of political power, an independent civil society, and practices of academic freedom. Our analysis highlights the theoretical value of polycentrism and self-governance beyond their more familiar role, of increasing accountability and competition in the provision of local public goods, towards facilitating effective national policy., (© The Author(s) 2023. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

A high-resolution chromosome microarray analysis was performed on 154 consecutive individuals enrolled in the DESTINY PWS clinical trial for Prader-Willi syndrome (PWS). Of these 154 PWS individuals, 87 (56.5%) showed the typical 15q11-q13 deletion subtypes, 62 (40.3%) showed non-deletion maternal disomy 15 and five individuals (3.2%) had separate unexpected microarray findings. For example, one PWS male had Klinefelter syndrome with segmental isodisomy identified in both chromosomes 15 and X. Thirty-five (40.2%) of 87 individuals showed typical larger 15q11-q13 Type I deletion and 52 individuals (59.8%) showed typical smaller Type II deletion. Twenty-four (38.7%) of 62 PWS individuals showed microarray patterns indicating either maternal heterodisomy 15 subclass or a rare non-deletion (epimutation) imprinting center defect. Segmental isodisomy 15 was seen in 34 PWS subjects (54.8%) with 15q26.3, 15q14 and 15q26.1 bands most commonly involved and total isodisomy 15 seen in four individuals (6.5%). In summary, we report on PWS participants consecutively enrolled internationally in a single clinical trial with high-resolution chromosome microarray analysis to determine and describe an unbiased estimate of the frequencies and types of genetic defects and address potential at-risk genetic disorders in those with maternal disomy 15 subclasses in the largest PWS cohort studied to date.

Prader-Willi syndrome is a complex neurodevelopmental genetic imprinting disorder with severe congenital hypotonia, failure to thrive with learning and behavioral problems, and hyperphagia with obesity developing in early childhood. Those with the typical 15q11-q13 Type I deletion compared with the smaller Type II deletion have more severe neurobehavioral problems and differ by the absence of four genes in the 15q11.2 BP1-BP2 region. Two of the genes encode magnesium transporters supporting brain and neurological function and we report on magnesium levels in the two deletion groups of PWS participants. We measured baseline plasma magnesium and analyzed data from a PWS cohort with and without the Type I or Type II deletion. Significantly lower plasma magnesium levels were found in PWS participants with the larger Type I deletion and more so with females with Type I deletion compared with females having the Type II deletion, although magnesium levels remained within normal range in both subgroups. Those with PWS and the larger 15q11-q13 Type I deletion were more clinically affected than those with the smaller Type II deletion. Two of the four genes missing in those with the larger deletion code for magnesium transporters and may impact magnesium levels. Our study showed lower magnesium levels in those with the larger deletion which could contribute to neurobehavioral differences seen in the two separate 15q11-q13 deletion subtypes and in addition affect both glucose and insulin metabolism impacting comorbidities but will require more research., (© 2022 Wiley Periodicals LLC.)

To evaluate the potential role of ATP-sensitive potassium (K ATP ) channel activation in the treatment of hyperphagic obesity, a PubMed search was conducted focused on the expression of genes encoding the K ATP channel, the response to activating the K ATP channel in tissues regulating appetite and the establishment and maintenance of obesity, the evaluation of K ATP activators in obese hyperphagic animal models, and clinical studies on syndromic obesity. K ATP channel activation is mechanistically involved in the regulation of appetite in the arcuate nucleus; the regulation of hyperinsulinemia, glycemic control, appetite and satiety in the dorsal motor nucleus of vagus; insulin secretion by β-cells; and the synthesis and β-oxidation of fatty acids in adipocytes. K ATP channel activators have been evaluated in hyperphagic obese animal models and were shown to reduce hyperphagia, induce fat loss and weight loss in older animals, reduce the accumulation of excess body fat in growing animals, reduce circulating and hepatic lipids, and improve glycemic control. Recent experience with a K ATP channel activator in Prader-Willi syndrome is consistent with the therapeutic responses observed in animal models. K ATP channel activation, given the breadth of impact and animal model and clinical results, is a viable target in hyperphagic obesity.

Advanced practice registered nurses (APRNs) are in an excellent position to provide leadership for advancing telehealth initiative. King's social system concepts of role, status, authority, power, and decision-making may be explored in this context. The authors of this article provide insight into the leadership opportunities in telehealth that exist for APRNs in current healthcare systems through a King perspective. The authors discuss some of the major challenges for APRNs in telehealth and how leadership may overcome some of those challenges.

Ribozymes are RNAs that can be designed to catalyze the specific cleavage or ligation of target RNAs. We have explored the possibility of using ribozymes in maize to downregulate the expression of the stearoyl-acyl carrier protein (Delta9) desaturase gene. Based on site accessibility and catalytic activity, several ribozyme constructs were designed and transformed into regenerable maize lines. One of these constructs, a multimer hammerhead ribozyme linked to a selectable marker gene, was shown to increase leaf stearate in two of 13 maize lines. There were concomitant decreases in Delta9 desaturase mRNA and protein. The plants with the altered stearate phenotype were shown to express ribozyme RNA. The ribozyme-mediated trait was heritable, as evidenced by stearate increases in the leaves of the R1 plants derived from a high-stearate line. The increase in stearate correlated with the presence of the ribozyme gene. A catalytically inactive version of this ribozyme did not produce any significant effect in transgenic maize. This is evidence that ribozymes can be used to modulate the expression of endogenous genes in maize.

We examined the time course and dose response of the triiodothyronine (T3) effect on mRNAs for sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) in cells of the human hepatoma line HepG2. After 7 h of exposure to a saturating dose of T3, SHBG mRNA was unchanged but increased to 1.5 +/- 0.1 times the unstimulated control at 22 h. Maximal stimulation (2.3 +/- 0.6) was observed at 2-3 days. Corticosteroid-binding globulin mRNA was unchanged for 22 h after exposure to T3 but diminished thereafter to 64% by day 3. At 3-4 days of exposure, the changes in both SHBG mRNA and CBG mRNA were dose-responsive to the T3 concentration. For both mRNAs, half-maximal response occurred between 10 and 20 pmol/l bioavailable T3. Cortisol-binding proteins secreted by HepG2 cells after 3 days in culture also were T3 dose-responsive. No re-uptake of secreted CBG by the cells was observed, suggesting that the T3 effect on CBG secretion occurs during production of the mature protein. These data suggest that T3 stimulates the expression of the SHBG gene and attenuates the expression of the CBG gene. The effects of T3 on these genes are consistent with the increase in circulating SHBG and decrease in circulating CBG observed in hyperthyroidism. The HepG2 cells may be a useful human cell line in which to study the diversity of the molecular mechanisms of T3 action.

In this study we have modified a micro Plasmodium falciparum in vitro growth inhibition assay to allow dissection of growth inhibition induced by test sera into two categories: inhibition of intracellular schizont growth and inhibition of uptake of merozoites into a second cohort of erythrocytes. This was achieved using morphology-controlled synchronised cultures with incubation times restricted to cover either ring to schizont development or schizont to ring development. Sera tested were obtained from a large prospective study of healthy residents of Madang, Papua New Guinea, who were carefully documented with respect to presence of malarial parasites in the blood, spleen size, age, sex and history of fever. In the ring to schizont assay sera from all the children tested inhibited parasitic growth by at least 20%, compared to only 10 of 39 adults tested (P less than 0.0005). In the schizont to ring assay 20 of 39 adult sera tested inhibited the uptake of 14C-isoleucine into P. falciparum protein compared to 3 of the 15 children's sera tested (P less than 0.01). These results are interpreted as reflecting a switch from non-specific mechanisms of resistance with increasing age.

In this study we have examined serum from patients with Plasmodium falciparum malaria, collected at the time of acute attack and 14 days later. We have also examined sequential samples of sera taken from children living in Madang Province, Papua New Guinea, an area endemic for malaria. The total amount of antibody directed against P. falciparum in acute phase sera was less than that found in matched controls. An in vitro assay measuring inhibition of penetration of uninfected erythrocytes by merozoites of P. falciparum revealed less inhibitory activity in acute phase sera than in matched controls. The longitudinal study of sera from village children demonstrated that non-specific inhibition of intracellular parasite growth was fairly stable, while merozoite inhibiting activity was unstable and varied with time. A cloned P. falciparum species has been used to directly demonstrate the specific growth enhancement by serum in vitro.

This article has reviewed some of the current methods of management of congenital problems in the upper extremity. Not all problems have been included in this review but some of the landmark advances in this field have been considered. The management of congenital anomalies may change significantly in the future.

A micro semiautomative assay of merozoite inhibition antibody has been developed, based on incorporation of radiolabeled isoleucine into parasite protein. The assay has been validated using 44 sera from healthy blood donors in Madang. Inhibition of uptake of label occurred in 43.2% of tests, while an enhancement of uptake was demonstrated in 4.7%. This assay has 'potential' for both seroepidemiological studies, and for providing a mechanism of biotyping wild isolates.

P. falciparum malaria was cultured in vitro in the presence of sera from patients with cerebral malaria, meningitis and also after chloroquine administration. Intra-erythrocytic parasite damage was seen by light and electron microscopy. The significance of the results is discussed with relevance to non-specific immune mechanisms, and the damage induced by these mechanisms compared with that from chloroquine.

The causes of irreducibility of juxta-epiphyseal fractures of the proximal phalanx are illustrated in a patient with button hole rent in the periosteum and extensor hood mechanism causing trapping of the distal fragment. The entrapment, in the manner of a Chinese finger trap, was aggravted by traction on the digit. Open reduction was necessary to reduce the fracture.