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.

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.

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.

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.

Nocturnal Olfactory Stimulation for Improvement of Sleep Quality in Patients With Posttraumatic Stress Disorder: A Randomized Exploratory Intervention Trial.

Posttraumatic stress disorder (PTSD) is characterized by sleep impairment and nightmares. As pleasant odors presented during sleep affect the emotional tone of dreams without inducing arousal, we investigated whether sleep patterns in PTSD can be improved via nocturnal olfactory stimulation. Participants were 40 inpatients with PTSD (n = 35 women; age range: 20-59 years) who completed a randomized, patient-blind, placebo-controlled trial. Baseline measurement for 5 consecutive nights was followed by a 5-night experimental intervention or placebo trial. During the intervention, patients received nocturnal stimulation with a pleasant odor (odor condition) or clean air (placebo condition) via an olfactometer that delivered inspiration-triggered stimuli in a nasal tube or via an odorized nasal clip. After each night, the patients completed standardized questionnaires that assessed sleep parameters and dream content. Each night, sleep efficiency, sleep onset latency, and wakefulness after sleep onset were monitored with a motion biosensor. Baseline assessment revealed that PTSD severity was associated with poorer sleep outcomes. An interaction effect showed that nocturnal odorization affected dream intensity. Post hoc tests revealed an improvement in the group that used the nasal clip as compared to baseline, d = 0.68. No negative effects were observed after odorization with the nasal clip. Considering the limited sample size, the study indicates that nocturnal olfactory stimulation may serve as a low-cost concomitant intervention to improve sleep quality in PTSD.

Spanish Abstracts by Asociación Chilena de Estrés Traumático (ACET) Estimulación Olfatoria Nocturna para Mejorar la Calidad del Sueño en pacientes con Trastorno por Estrés Postraumático: Un ensayo de intervención exploratorio aleatorizado ESTIMULACIÓN OLFATORIA NOCTURNA EN PTSD El trastorno de estrés postraumático (TEPT) se caracteriza por trastornos del sueño y pesadillas. Como los olores agradables que se presentan durante el sueño afectan el tono emocional de los sueños sin inducir alerta, exploramos si los patrones de sueño en el TEPT pueden mejorarse a través de la estimulación olfatoria nocturna. Los participantes fueron 40 pacientes hospitalizados con TEPT (n = 35 mujeres; rango de edad: 20-59 años) que completaron un ensayo aleatorizado, ciego para los pacientes, controlado con placebo. La medición de línea base durante cinco noches consecutivas fue seguida por una intervención experimental de 5 noches o un ensayo con placebo. Durante la intervención, los pacientes recibieron estimulación nocturna con un olor agradable (condición de olor) o aire limpio (condición de placebo) a través de un olfatómetro que administró estímulos que gatillan-inspiración en un tubo nasal o mediante un clip nasal odorizado. Después de cada noche, los pacientes completaron cuestionarios estandarizados que evaluaron los parámetros de la calidad del sueño y del contenido de los sueños. Cada noche, la eficacia del sueño, la latencia del inicio del sueño y la vigilia después del inicio del sueño se controlaron con un biosensor de movimiento. La evaluación de línea base reveló que la gravedad del TEPT se asoció con resultados de sueño más deficientes. Un efecto de interacción mostró que la odorización nocturna afectó la intensidad del sueño. Pruebas post hoc revelaron una mejoría en el grupo que usó el clip nasal en comparación con la línea base, d = 0.68. No se observaron efectos negativos después de la odorización con el clip nasal. Teniendo en cuenta el tamaño limitado de la muestra, el estudio indica que la estimulación olfatoria nocturna puede servir como una intervención concomitante de bajo costo para mejorar la calidad del sueño en el TEPT.

Human Leukocyte Antigen similarity decreases partners' and strangers' body odor attractiveness for women not using hormonal contraception.

The Human Leukocyte Antigen (HLA) is a gene complex that encodes important elements of the human immune system. HLA profile is communicated via olfaction and interindividual diversity is assumed to be advantageous for mate choice. Additionally, HLA diversity appears to enhance satisfaction and sexual attraction in existing romantic partnerships. However, whether this effect is transmitted via body odors and whether it results in an attraction towards HLA-dissimilar individuals and/or an avoidance of HLA-similar ones remains unclear. In the present study, we genotyped couples and asked each participant to rate a body odor sample from their partner and from three strangers of the opposite sex who expressed a similar or dissimilar HLA-B and HLA-C genotype. We found no statistically significant preference for HLA similarity or dissimilarity in men. Among women, the observed effects differed depending on hormonal contraception status. Like men, women on hormonal contraception did not exhibit significant HLA-related preferences. However, for women not using hormonal contraceptives, odors from HLA-B and HLA-C similar donors were significantly less attractive than those from HLA-dissimilar donors, regardless of whether the samples were from a partner or a stranger. Our findings support the hypothesis that HLA similarity is perceived via body odors and that such similarity affects human attraction. This mechanism may serve an evolutionarily adaptive function in preventing prospective offspring from having decreased immunocompetence, or decreasing the chance of kin mating.

[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.

The scent of cuteness-neural signatures of infant body odors.

The smell of the own baby is a salient cue for human kin recognition and bonding. We hypothesized that infant body odors function like other cues of the Kindchenschema by recruiting neural circuits of pleasure and reward. In two functional magnetic resonance imaging studies, we presented infantile and post-pubertal body odors to nulliparae and mothers (N = 78). All body odors increased blood-oxygen-level-dependent (BOLD) response and functional connectivity in circuits related to olfactory perception, pleasure and reward. Neural activation strength in pleasure and reward areas positively correlated with perceptual ratings across all participants. Compared to body odor of post-pubertal children, infant body odors specifically enhanced BOLD signal and functional connectivity in reward and pleasure circuits, suggesting that infantile body odors prime the brain for prosocial interaction. This supports the idea that infant body odors are part of the Kindchenschema. The additional observation of functional connectivity being related to maternal and kin state speaks for experience-dependent priming.

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.

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.

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.

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.

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.

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.

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.

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.