Body odor samples from infants and post-pubertal children differ in their volatile profiles.

Body odors change during development, and this change influences the interpersonal communication between parents and their children. The molecular basis for this chemical communication has not been elucidated yet. Here, we show by combining instrumental and sensory analyses that the qualitative odorant composition of body odor samples is similar in infants (0-3 years) and post-pubertal children (14-18 years). The post-pubertal samples are characterized by higher odor dilution factors for carboxylic acids and by the presence of 5α-androst-16-en-3-one and 5α-androst-16-en-3α-ol. In addition to the olfaction-guided approach, the compounds 6-methylhept-5-en-2-one (6MHO), geranyl acetone (GA) and squalene (SQ) were quantified. Both age groups have similar concentrations of 6MHO and GA, whereas post-pubertal children tend to have higher concentration of SQ. In conclusion, sexual maturation coincides with changes to body odor chemical composition. Whether those changes explain differences in parental olfactory perception needs to be determined in future studies with model odors.

A placebo-controlled, double-blind study evaluating the effect of orally administered polyunsaturated fatty acids on the oclacitinib dose for atopic dogs.

BACKGROUND: Supplementation of polyunsaturated fatty acids (PUFA) enables dose reduction of prednisolone and ciclosporin in canine atopic dermatitis (cAD). OBJECTIVE: To determine if oral administration of PUFA reduces the dose of oclacitinib in cAD. ANIMALS: Twenty-two client-owned dogs with cAD receiving oclacitinib. MATERIALS AND METHODS: Dogs received a fish oil product (PUFA) or paraffin oil (placebo) for 16 weeks. Owners adjusted the oclacitinib dose according to daily pruritus assessments. On Day (D)0, D56 and D112, Canine Atopic Dermatitis Extent and Severity Index, fourth iteration (CADESI-04), pruritus Visual Analog Scale (PVAS), quality-of-life score (QoL), Global Assessment (GA), quality-of-coat (QoC) and adverse events were recorded. RESULTS: Mean daily oclacitinib dose was significantly reduced in the PUFA group from 0.51 ± 0.20 mg/kg/24 h (D0) to 0.19 ± 0.14 mg/kg/24 h (D85-112; p < 0.00001) and not in the placebo group (D0: 0.70 ± 0.33 mg/kg/24 h; D85-112: 0.53 ± 0.35 mg/kg/24 h, p = 0.5422). CADESI-04 did not change over time or differ between groups. PVAS was significantly lower in the PUFA group (2.8 ± 1.5) compared to placebo (4.2 ± 1.6) at D112 (p = 0.0375). QoL and QoC improved only in the PUFA group (QoL: D0: 20 ± 7, D112: 12 ± 5, p = 0.0057; QoC: D0: 0 ± 0.5, D112: 1 ± 0.5, p = 0.0410). GA on D112 was higher in the PUFA group (p = 0.008). No adverse events were observed. CONCLUSION: Oral supplementation of PUFA allowed dose reduction of oclacitinib and improved PVAS, QoL, QoC and GA. The use of PUFA is recommended and was safe in the atopic study dogs receiving oclacitinib.

Body odours as putative chemosignals in the father-child relationship: New insights on paternal olfactory kin recognition and preference from infancy to adolescence.

Children's body odours are effective chemical cues in the parent-child relationship. Mothers can recognize the odour of their child and prefer this odour over that of unfamiliar children. This effect is mediated by genetic similarity and developmental stage and is therefore suited to promote parental care at pre-pubertal stage, while facilitating incest avoidance at (post-)pubertal stage. The present study tested whether similar mechanisms apply to fathers. Therefore n = 56 fathers evaluated body odour samples of their own and of unfamiliar children in varying genetic and developmental stages. Genetic status was determined by human leucocyte antigen (HLA) profiling, developmental status by standardized assessment of pubertal status and steroid hormone concentration (estradiol, testosterone). Similar to mothers, fathers identified their own child's body odour above chance and preferred that odour. The paternal preference did not relate to HLA similarity but decreased with increasing age of the child. The decline was associated with higher pubertal stages in daughters only, which supports the hypothesis of odour-mediated incest prevention in opposite-sex parent-child dyads.

[Intradermal and serologic testing for insect bite hypersensitivity in a Dahomey-Ox]. / Intradermaler und serologischer Allergietest zur Abklärung einer Insektenstich-Hypersensitivität bei einem Dahomey-Ochsen.

This case report describes an eosinophilic dermatitis on the prepuce of a Dahomey-Ox caused by an insect bite hypersensitivity against Culicoides spp. To the best of the authors' knowledge, this is the first report describing intradermal allergy and serological testing in cattle.

Validation of Dual-Action Chemo-Radio-Labeled Nanocarriers with High Efficacy against Triple-Negative Breast Cancer.

Identification and selectivity of molecular targets with prolonged action for difficult-to-target cancer such as triple-negative breast cancer (TNBC) represent a persisting challenge in the precision delivery of therapeutics. In the quest to target undruggable sites, this study validates the bioavailability of polydopamine-sealed mesoporous silica nanocarriers (PDA-mSiO2) for in vivo drug delivery to TNBC. For controlled transport and release, the chemotherapeutic drug doxorubicin was encapsulated in mSiO2 nanocarriers coated with a PDA layer serving as a stimuli-responsive gatekeeper or seal. For unifying targeting and treatment modalities, these nanocarriers were covalently conjugated to a macrocyclic chelator (DOTA) and folate (FA-mSiO2.) that enabled incorporation of radionuclides and identification of FR Alpha (FolRα) receptors present on TNBC cells. The robust chemical design of FA- and DOTA-functionalized PDA-coated mSiO2 nanocarriers constitutes mild reaction conditions to avoid the loss of surface-bound molecules. The radiolabeling studies with the theranostic pair 68Ga and 177Lu showed quantitative trends for radiochemical efficacy and purity. Nanocarriers equipped with both radiolabels and affinity ligands were optimally stable when incubated with human serum for up to 120 h (177Lu), demonstrating hydrophilicity with a partition coefficient (log P) of -3.29 ± 0.08. Specifically, when incubated with TNBC cells, the cells received significant FA-mSiO2 carriers, demonstrating efficient carrier internalization and time-dependent uptake. Moreover, in vivo results visualize the retention of drug-filled carriers at the tumor sites for a long time, which holds promise for therapeutic studies. This research work demonstrates for the first time the successful dual conjugation of nanocarriers through the colocation of radionuclides and anticancer drugs that is promising for both live molecular imaging and enhanced therapeutic effect for TNBC.

An integrative review: Human chemosensory communication in the parent-child relationship.

Body odors serve as signals of kinship, with parents exhibiting a preference for the scent of their infants, and vice versa. The reciprocal perception of body odors can promote bonding through two mechanisms. Firstly, as an indirect pathway, through associative chemosensory learning, which leads to changes in proximity-seeking behaviors. Secondly, as a direct pathway, by eliciting the display of positive emotions, thereby reinforcing the mutual bond. Both mechanisms weaken as the child undergoes development due to changes in body odor expression and perception. This comprehensive review provides an overview of the current literature on chemosignals in the parent-child relationship, highlighting their significance in facilitating dyadic communication throughout the developmental span. Furthermore, future research perspectives are outlined to gain a better understanding of these benefits and, on the long run, derive potential interventions to strengthen parent child attachment.

Identification of an ADAMTS2 frameshift variant in a cat family with Ehlers-Danlos syndrome.

We investigated 4 European domestic shorthair kittens with skin lesions consistent with the dermatosparaxis type of the Ehlers-Danlos syndrome, a connective tissue disorder. The kittens were sired by the same tomcat but were born by 3 different mothers. The kittens had easily torn skin resulting in nonhealing skin wounds. Both clinically and histologically, the skin showed thin epidermis in addition to inflammatory changes. Changes in collagen fibers were visible in electron micrographs. The complete genome of an affected kitten was sequenced. A one base pair duplication leading to a frameshift in the candidate gene ADAMTS2 was identified, p.(Ser235fs*3). All 4 affected cats carried the frameshift duplication in a homozygous state. Genotypes at this variant showed perfect cosegregation with the autosomal recessive Ehlers-Danlos syndrome phenotype in the available family. The mutant allele did not occur in 48 unrelated control cats. ADAMTS2 loss-of-function variants cause autosomal recessive forms of Ehlers-Danlos syndrome in humans, mice, dogs, cattle, and sheep. The available evidence from our investigation together with the functional knowledge on ADAMTS2 in other species allows to classify the identified ADAMTS2 variant as pathogenic and most likely causative variant for the observed Ehlers-Danlos syndrome.

Neural Stem Cells as Carriers of Nucleoside-Conjugated Nanogels: A New Approach toward Cell-Mediated Delivery.

Neural stem cells (NSCs) present attractive natural drug delivery systems (DDSs). Their migratory potential enables crossing of the blood-brain barrier and efficient and selective accumulation near malignant cells. Here, we present the potential of NSCs as DDSs for nucleoside analogue-conjugated nanogels (NGs). Two different approaches were investigated: the intracellular loading and extracellular cell surface decoration with NGs. For both designs, the tumor-specific migratory potentials of NSCs remained unchanged; however, the intracellular loading showed a shorter NG retention. The cell surface decoration protocol yielded a high loading capacity of 100% after 1 h and a prolonged drug retention. A redox-sensitive linker between NGs and the nucleoside analogue 5-ethynyl-2'-deoxycytidine (EdC) allowed a tumor environment-specific drug release and its efficient and preferential incorporation into the DNA of the tumor cells. Interestingly, the tumor-trafficking potentials of NSCs were significantly potentiated by irradiation of tumor cells. In conclusion, this study indicates the potentials of cell surface-decorated NSCs as DDSs for tumor-specific release, cellular uptake, and incorporation of EdC into DNA.

Technological Pathways to Produce Compressed and Highly Pure Hydrogen from Solar Power.

Hydrogen (H2 ) produced from renewables will have a growing impact on the global energy dynamics towards sustainable and carbon-neutral standards. The share of green H2 is still too low to meet the net-zero target, while the demand for high-quality hydrogen continues to rise. These factors amplify the need for economically viable H2 generation technologies. The present article aims at evaluating the existing technologies for high-quality H2 production based on solar energy. Technologies such as water electrolysis, photoelectrochemical and solar thermochemical water splitting, liquid metal reactors and plasma conversion utilize solar power directly or indirectly (as carbon-neutral electrons) and are reviewed from the perspective of their current development level, technical limitations and future potential.

Determination of amino acid content, fatty acid profiles, and phenolic compounds in non-conventional edible fruits of seven species of palm trees (Arecaceae) native to the southern half of South America.

The fruits of palm trees (Arecaceae) are a very important food source for fauna and for humans, despite the still incipient role of these fruits in conventional diet. Seven palm tree species (plus one variety) that are native to the southern half of South America located east of the Andes (Argentina, Paraguay, Uruguay, and the southern states of Brazil) were studied. For the first time, the fatty acid profiles of palm seeds and the content of both amino acids and phenolic compounds present in the pulp (yellowish fleshy mesocarps) of the fruits were determined. High-performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS) was used to screen and quantify thirty-two phenols and HPLC was used to determine the amino acid contents and fatty acids profiles of the species. Twenty-five percent of the fatty acids in the seeds of B. lallemantii, Butia odorata (var. pulposa), B. witeckii, and Syagrus romanzoffiana were found to be unsaturated. One species (B. lallemantii) had a high and well-balanced amino acid content (28,900 mg/kg), while six species (B. odorata, B. catarinensis, B. witeckii, Euterpe edulis, and Syagrus romanzoffiana) contained more than 14,000 mg/kg of amino acids. A high content of the phenolic compounds ferulic acid, luteolin, quercetin-3-rutinoside, isoquercetin, and isorhamnetin were found in many species, most notably in B. odorata, B. catarinensis, and B. witeckii.

PARP targeted Auger emitter therapy with [125I]PARPi-01 for triple-negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) lacks biomarkers for targeted therapy. Auger emitters display the best therapeutic effect, if delivered directly into the nucleus proximal to DNA. The nuclear protein Poly (ADP-ribose)-Polymerase 1 (PARP1) is a suitable target against which few inhibitors (PARPi) are clinically approved for treatment of breast cancer with germline BRCA mutation (BRCAmut). In this study, a theranostic approach was investigated in a TNBC xenografted mouse model by radiolabelling a close derivative of a PARPi Olaparib (termed PARPi-01) with the Auger emitters 123/125I. METHODS: TNBC cell line MDA-MB-231 was subcutaneously implanted in female NOD/SCID mice. At a tumour size of ~ 500mm3, [123I]PARPi-01 was administered intravenously, and SPECT/CT images were obtained at 4 h or 24 h post injection (p.i). A therapy study was performed with [125I]PARPi-01 in 4 doses (10 MBq/dose, 10 days apart). Tumour growth was monitored by CT scans longitudinally once per week. Upon reaching study endpoint, tissues were harvested and stained with TUNEL assay for detection of apoptosis induction. RESULTS: SPECT/CT images showed rapid hepatobiliary tracer clearance at 4 h post injection (p.i.). Retention in thyroid at 24 h p.i. suggested tracer deiodination in vivo. The tumour and liver uptake were 0.2%ID/g and 2.5%ID/g, respectively. The tumour: blood ratio was 1.3. Endogenous therapy induced a significant delay in tumour growth (doubling time increased from 8.3 to 14.2 days), but no significant survival advantage. Significantly higher apoptosis ratio was observed in [125I]PARPi-01 treated tumour tissues. No radiotoxicity was detected in the liver and thyroid. CONCLUSION: Considering the radio-cytotoxic effect in the tumour tissue and a delay on tumour doubling time, [125I]PARPi-01 presents a potential radiotherapeutics for treatment of TNBC. Improvements to overcome the suboptimal pharmacokinetics are necessary for its potential clinical application.

Vibration as a pitfall in pyrosequencing analyses.

Since methylation analysis has become an important tool in forensic genetics, the reliability and credibility of the method must be ensured. After a successful validation and establishment of several pyrosequencing assays using a PyroMark® Q48 Autoprep instrument (Qiagen, Hilden, Germany), we decided to expand the method further purchasing a second instrument. But after initializing this second instrument side by side with the first, the majority of analyses failed (97 samples of 133 samples (73%)). The number of error messages increased rapidly and the average RFU values decreased. After purchasing two anti-vibration weighing tables for the PyroMark® instruments and repeating the analyses under the same conditions and with identical samples the results improved considerably, 115 samples of 130 samples (88%) showed successful and reproducible results. These findings demonstrate the impact of vibrations and percussions on PyroMark® Q48 Autoprep performance and the reliability of methylation analyses.

Body Odours Sampled at Different Body Sites in Infants and Mothers-A Comparison of Olfactory Perception.

Body odours and their importance for human chemical communication, e.g., in the mother-child relationship, are an increasing focus of recent research. Precise examination of sampling methods considering physiology and feasibility aspects in order to obtain robust and informative odour samples is therefore necessary. Studies comparing body odour sampling at different body sites are still pending. Therefore, we sampled axilla, breast, and head odour from 28 mother-infant dyads and examined whether odour perception differs with regard to the body site. The participating mothers were asked to evaluate their own and their infant's body odour samples, as well as odours of two unfamiliar mother-infant dyads. We tested whether maternal pleasantness and intensity evaluation, as well as recognition ability of the odours differed between the body sites. In infants, the head odour exhibited slightly lower pleasantness ratings than axilla and breast, and intensity ratings did not differ between body sites. In mothers, body site affected intensity ratings but not pleasantness ratings, as the breast odour was rated as less intense compared with head and axilla. Across all body sites, mothers rated the own and their infant's odour as less intense when compared with unfamiliar samples. Recognition ability did not differ between body sites, and in line with previous studies, mothers were able to recognize their own and their own infant's odour above chance. In sum, our study extends the previous methodological repertoire of body odour sampling and indicates that the axilla, breast, and head of adults as well as infants serve as informative odour sources.

[Predictors of process-related and structuring parental support during distance learning due to Corona-pandemic]. / Prädiktoren von prozessbezogener und strukturierender elterlicher Unterstützung während des (coronabedingten) Distanzunterrichts.

School closure due to Corona-pandemic shifted school learning into the families. Pupils were faced with the task to organize learning and the use of learning time more independently. The children were primarily supported by parents in aspects of organization and learning content. Based on previous research on parental homework support and educational partnerships, it can be assumed that both the structuring and process-related learning support provided by parents depends on socio-demographic characteristics of the family, but is also associated with characteristics of the child (e.g., age, learning behavior) and the perceived school learning support (teacher commitment, level of requirements). These associations were investigated by regression analysis on the basis of data from a standardized online survey with N = 6685 parents of children at secondary schools in the German federal state of North Rhine-Westphalia. The findings speak in favor of adaptive learning support for parents, which is less intensive for older and female students with favorable learning behavior than for younger and male students with unfavorable learning behavior. School-based learning guidance also contributes to the prediction of parental behavior, with committed teacher behavior contributing to increased support for the child, especially in families with lower school leaving certificates of (surveyed) parents.

Human olfactory dysfunction: causes and consequences.

The sense of smell essentially contributes to social communication, guides nutrition behaviour and elicits avoidance towards environmental hazards. Olfactory smell impairment may hence entail severe consequences for affected individuals. Compared with sensory loss in other modalities, reduced olfactory function is often unnoticed by those affected and diagnosed late. Those patients seeking help frequently suffer from long-term impairments resulting in reduced well-being and quality of life. The current review provides an overview of aetiology, prevalence and specifics of diagnostics in acquired and congenital olfactory loss and focusses on short- and long-term consequences. Compensation strategies are elaborated, and treatment options are mentioned. Individual characteristics associated with the development of serious mental health impairment are discussed in order to help practitioners identifying populations at risk.

Marriage does not relate to major histocompatibility complex: a genetic analysis based on 3691 couples.

Optimization of chances for healthy offspring is thought to be one of the factors driving mate choice and compatibility of the major histocompatibility complex (MHC) is assumed to determine the offspring's fitness. While humans have been claimed to be able to perceive information of MHC compatibility via the olfactory channel, it remains unknown whether humans use such information for mate choice. By investigation of 3691 married couples, we observed that the high polymorphism of MHC leads to a low chance for homozygous offspring. MHC similarity between couples did not differ from chance, we hence observed no MHC effect in married couples. Hormonal contraception at the time of relationship initiation had no significant effect towards enhanced similarity. A low variety of alleles within a postcode area led to a higher likelihood of homozygous offspring. Based on this data, we conclude that there is no pattern of MHC dis-assortative mating in a genetically diverse Western society. We discuss the question of olfactory mate preference, in-group mating bias and the high polymorphism as potential explanations.

Body odours as a chemosignal in the mother-child relationship: new insights based on an human leucocyte antigen-genotyped family cohort.

Mothers are able to identify the body odour (BO) of their own child and prefer this smell above other BOs. It has hence been assumed that the infantile BO functions as a chemosignal promoting targeted parental care. We tested this hypothesis and examined whether children's BOs signal genetic similarity and developmental status to mothers. In addition, we assessed whether BOs facilitate inbreeding avoidance (Westermarck effect). In a cross-sectional design, N = 164 mothers participated with their biological children (N = 226 children, aged 0-18 years) and evaluated BO probes of their own and four other, sex-matched children. Those varied in age and in genetic similarity, which was assessed by human leucocyte antigen profiling. The study showed not only that mothers identified and preferred their own child's BO, but also that genetic similarity and developmental status are transcribed in BOs. Accordingly, maternal preference of their own child's odour changes throughout development. Our data partly supported the Westermarck effect: mothers' preference of pubertal boys' BOs was negatively related to testosterone for the own son, but not for unfamiliar children. This article is part of the Theo Murphy meeting issue 'Olfactory communication in humans'.

Children's Body Odors: Hints to the Development Status.

Mothers can recognize their own children by body odor. Besides signaling familiarity, children's body odors may provide other information relevant to maternal caregiving behavior, such as the child's developmental status. Thus, we explored whether mothers are able to classify body odors on pre- vs. postpubertal status above chance levels. In total, 164 mothers were presented with body odor samples of their own and four unfamiliar, sex-matched children who varied in age (range 0-18 years). Pubertal status was measured by (a) determining the child's steroid hormone level and (b) parental assessment of the child's developmental stage using the Pubertal Development Scale. Mothers classified developmental status with an accuracy of about 64%. Maternal assessments were biased toward pre-puberty. Classification was predicted by perceptual evaluation of the body odor (i.e. intensity and pleasantness) and by the child's developmental stage, but not by hormones. In specific, mothers with pubertal-aged children classified body odors using the child's developmental status, whereas mothers with younger children only classified body odors using perceptual information (i.e. intensity and pleasantness). Our data suggests that body odors convey developmental cues, but how this developmental information is manifested in body odor remains unclear.