A phosphorylation assay in vitro showed markedly reduced autophosphorylation in cells expressing mutations. According to ACMG criteria, both mutations were pathogenic. A radiological investigation revealed typical white matter lesions in all cases. There was inter-individual diversity in the loss of cognitive, motor-neuronal, and extrapyramidal functions.

Including the present cases, currently three CSF1R mutations are known in Sweden. We present a visualization tool to describe the clinical diversity, with potential use for longitudinal follow-up for this and other leukoencephalopathies.

Including the present cases, currently three CSF1R mutations are known in Sweden. We present a visualization tool to describe the clinical diversity, with potential use for longitudinal follow-up for this and other leukoencephalopathies.Partial nitration-anammox is a resource-efficient pathway for nitrogen removal from wastewater. However, the advantages of this nitrogen removal technology may be counter-acted by the emission of N2 O, a potent greenhouse gas. In this study, mathematical modelling was applied to analyse N2 O formation and emission dynamics and to develop N2 O mitigation strategies for a one-stage partial nitritation-anammox granular sludge reactor. Dynamic model calibration for such a full-scale reactor was performed, applying a one-dimensional biofilm model and including several N2 O formation pathways. Simultaneous calibration of liquid phase concentrations and N2 O emissions leads to improved model fit compared to their consecutive calibration. The model could quantitatively predict the average N2 O emissions and qualitatively characterize the N2 O dynamics, adjusting only seven parameter values. The model was validated with N2 O data from an independent data set at different aeration conditions. Nitrifier nitrification was identified as the dominating N2 O formation pathway. Off-gas recirculation as a potential N2 O emission reduction strategy was tested by simulation and showed indeed some improvement, be it at the cost of higher aeration energy consumption.Susceptibility to stress has long been considered important for the development of substance use disorders. Nonetheless, behavioral and physiological responses to stress are highly variable, making it difficult to identify the individuals who are most likely to abuse drugs. In the present study, we employed a comprehensive battery of tests for negative valence behaviors and nociception to identify individuals predisposed to opioid seeking following oral opioid self-administration. Furthermore, we examined how this profile was affected by a history of stress. We observed that mice receiving foot shock stress failed to exhibit a preference for sucrose, showed increased immobility in the forced swim task, and exhibited mechanical hypersensitivity when compared to controls. When considering these behaviors in light of future fentanyl-seeking responses, we observed that heightened mechanical sensitivity corresponded to higher opioid preference in mice with a history of stress, but not controls. Moreover, we were surprised to discover that paradoxically high sucrose preferences predicted fentanyl preference in shock mice, while signs of anhedonia predicted fentanyl preference in controls. Taken together, these results indicate that stress can act as a physiological modulator, shifting profiles of opioid abuse susceptibility depending on an individual’s history.The pink teeth phenomenon was first reported in people who died by hanging or drowning in 1829. In recent years, there have been many reports that the occurrence of postmortem pink teeth is closely related to the condition of surroundings and time after death rather than to the cause of death, as had previously been thought. We observed pink teeth in 68 of 324 unidentified cadavers autopsied during 2015-2021, and we investigated the relationship of pink teeth with age, sex, cadaveric condition, time after death, tooth type, and cause of death. The results showed no significant differences in the occurrence of pink teeth according to sex or place of discovery (indoors, outdoors, or in water). Pink teeth tended to be observed below the age of 60 years. In the 68 cases with pink teeth, 29.1% of all vital teeth were affected, with the anterior teeth being most common. No evidence was found that supported an association between pink teeth and cause of death. These results are largely consistent with recent reports on postmortem pink teeth. As it stands, the pink teeth phenomenon may be nonspecific and must not be misinterpreted in medico-legal investigations. This case series provides further evidence supporting recent reports and contributes to clarifying in greater detail the mechanisms of the coloration and fading of pink teeth.Childhood obesity continues to rise in the United States and, with it, the off-label use of metformin for weight loss. The influence of age and obesity on the drug’s disposition and exposure has not previously been studied using a mechanistic framework. Here, an adult physiologically based pharmacokinetic (PBPK) model of metformin was scaled to pediatric populations without obesity, with overweight/obesity, and with severe obesity; a published virtual population of children and adolescents with obesity was leveraged during model evaluation. When the pediatric model was simulated in groups aged 10 to 18 years, oral clearance following 1000 mg of metformin was higher (≈1200 mL/min) in those with obesity and severe obesity compared to the groups without and with overweight (≈1000 mL/min). In addition, simulated area under the concentration-time curve in older children and adolescents with obesity and severe obesity was comparable to that in adults with a similar dose-exposure relationship. Overall, simulations using the pediatric PBPK model support the use of adult doses of metformin in older children and adolescents with obesity. Moreover, the virtual population of children and adolescents with obesity offers a valuable tool to facilitate development of pediatric PBPK models for studying populations with obesity and, in turn, contribute information to inform drug labeling in this special population.The planthopper resistance gene Bph6 encodes a protein that interacts with OsEXO70E1. EXO70 forms a family of paralogues in rice. We hypothesized that the EXO70-dependent trafficking pathway affects the excretion of resistance-related proteins, thus impacting plant resistance to planthoppers. Here, we further explored the function of EXO70 members in rice resistance against planthoppers. We used the yeast two-hybrid and co-immunoprecipitation assays to identify proteins that play roles in Bph6-mediated planthopper resistance. The functions of the identified proteins were characterized via gene transformation, plant resistance evaluation, insect performance, cell excretion observation and cell wall component analyses. We discovered that another EXO70 member, OsEXO70H3, interacted with BPH6 and functioned in cell excretion and in Bph6-mediated planthopper resistance. We further found that OsEXO70H3 interacted with an S-adenosylmethionine synthetase-like protein (SAMSL) and increased the delivery of SAMSL outside the cells. The functional impairment of OsEXO70H3 and SAMSL reduced the lignin content and the planthopper resistance level of rice plants. Our results suggest that OsEXO70H3 may recruit SAMSL and help its excretion to the apoplast where it may be involved in lignin deposition in cell walls, thus contributing to rice resistance to planthoppers.Chlorophyll-a derivatives possessing a substituted methylene group at the 132 -position were prepared by the mixed aldol condensation of methyl 3-hydroxymethyl-pyropheophorbide-a with aldehydes bearing a methyl, p-nitro/cyanophenyl, or pentafluorophenyl group. Their electronic absorption spectra were dependent on the substituents at the methylene terminal. The Soret bands were broadened by increasing the group electronegativity of the substituents, which was ascribable to the charge transfer from the core chlorin to the peripheral substituent in a molecule. Although their Qy absorption and fluorescence emission bands resembled each other, the emission intensities decreased with an increase in the electronegativity because of intramolecular electron transfer quenching. Some of their zinc complexes self-aggregated in a less polar organic solvent to give red-shifted and broadened absorption bands with intense circular dichroism couplets, which were similar to those of bacteriochlorophyll-c/d aggregates in natural chlorosomes as the main light-harvesting antennas of green photosynthetic bacteria and their models. The J-aggregation was suppressed with an enhancement in the size of the 132 -substituents.In his 1959 book, Africa Its Peoples and Their Culture History, George P. Murdock suggested that a Malaysian complex of crops dispersed to Africa in ancient times across the Indian Ocean along the Sabaean Lane. The Malaysian complex comprised bananas, sugarcane, taro, three yam species, rice, Polynesian arrowroot, breadfruit, coconut, areca palm, and betel leaf. Except for rice, arrowroot, and potentially taro, most of these crops were domesticated in the Island Southeast Asia-New Guinea region, from where they dispersed to Africa. Our reassessment of agronomic, archaeological, classical, genetic, and historical sources shows that we need to go beneath standard historical narratives to recover a much more ancient and complex history of crop introductions to Africa. Despite considerable uncertainty and fragmented research, we were able to conclude that the Malaysian complex of crops did not arrive in Africa as a complete assemblage at one time or along one route. Multiple lines of evidence suggest that these crops arrived in Africa at different times and followed different pathways of introduction to the continent.Not required for Clinical Vignette.Not required for Clinical Vignette.Not required for Clinical Vignette.

Metabolic syndrome (MetS), which includes abdominal obesity, hypertension, hypertriglyceridaemia, low high-density lipoprotein cholesterol and elevated fasting plasma glucose, is now well understood. The prevalence of MetS is increasing all over the world. Central obesity is the main and the most common component of MetS. The most simple, practical, and frequently used tool for assessing body weight is body mass index. The aim of our study was to show the correlation between waist circumference (WC) and BMI in women with MetS depending on its components.

It was a study of 36-month duration (2016-2019) conducted in University Hospital No. 1 in Bydgoszcz, Poland. The study included 696 women with diagnosed MetS according to the 2009 International Diabetes Federation criteria.

In the study group, WC was found to be significantly correlated with BMI according to the arterial hypertension, T2DM, IFG, lower HDL-C, and higher TG level.

We should consider changing the WC guidelines for Europeans, but for this we need more prospective studies.

We should consider changing the WC guidelines for Europeans, but for this we need more prospective studies.

This review aimed to synthesize evidence on the impact of the COVID-19 lockdown on the glycaemic control, physical activity, and diet of diabetic patients.

Two electronic databases (PubMed and Scopus) were searched from January 2020 to February 2021. A total of 161 unique records were retrieved. Out of these, 25 articles met the eligibility criteria and were included in the final review. The quality of the studies was assessed by using the modified Newcastle-Ottawa Quality Assessment Scale for observational studies.

Out of the 25 studies included in the review, 18 (72%) were cross sectional, 5 (20%) were retrospective analyses, and 2 (8%) were cohort studies. Thirteen studies included type I diabetics, 8 studies included type2 diabetics, and 4 studies included both. In the quality assessment, 17 (68%) of the studies met the criteria of satisfactory quality. Overall glycaemic parameters were improved during the lockdown. Dietary patterns were affected during the lockdown, but the direction of change- either negative or positive- could not be inferred.