The Daniel Stern concept of the motherhood constellation describes a distinctive psychic organization that emerges in the transition to motherhood, structured by 3 relational discourses and 4 thematic concerns: safeguarding infant life and growth, establishing primary relatedness, securing a matrix of support, and reorganizing maternal identity. Formulated in the mid-1990s, this framework preceded the pervasive integration of smartphones, social media, and artificial intelligence (AI) into everyday life. Contemporary mothers now care for infants in environments saturated by online information, connectivity, and AI-mediated support, raising questions about how these factors participate in and reshape the Stern architecture. This theoretical paper argues that smartphones and AI function not as neutral tools but as systemic actors within the motherhood constellation. Drawing on the Stern model, attachment theory, mentalization research, ecological perspectives, sociotechnical theory, and empirical work on technoference, maternal smartphone use, digital parenting, online maternal communities, and AI-based mental health interventions, we conceptualize digital technologies as entities whose affordances co-structure maternal psychic life. Available findings indicate that they simultaneously expand access to information and support, introduce interactional disruptions, and create new, partially algorithmic matrices of support, with effects moderated by patterns of use, maternal reflective functioning, child characteristics, platform design, and socio-structural conditions. We propose a technologically mediated motherhood constellation, in which smartphones and AI enter all 3 discourses (mother-own-mother, mother-self-as-mother, and mother-infant) and all 4 themes. Rather than asking whether technology is "good" or "bad" for motherhood, we outline a spectrum from technology-enhanced to technology-disrupted constellations and derive implications for clinical practice, research, technology design, and social policy.
Protein kinases (PKs) are enzymes that catalyze phosphorylation of protein substrates involved in a wide variety of biological signalling pathways. PKs can be distinguished based on their mechanism of action and their regulation. They are associated with numerous pathologies, thereby constituting attractive biomarkers and targets for development of therapeutics. Given their importance, a wide variety of strategies and technologies have been devised for their detection, their quantification, and for studying their dynamic behavior, from radioactive and antibody-based approaches to biochemical, kinomic, and biosensing technologies. A wide variety of fluorescent biosensors have been tailored to report on PK activities in vitro and for imaging purposes. These tools allow researchers to monitor PK activities in a highly sensitive and dynamic fashion in complex samples, providing new avenues for investigating PK behavior in native conditions and following stimulation or inhibition with drugs, thereby providing functional information which complements genetic, transcriptomic, or proteomic approaches. This review focuses on the different families of PKs and on fluorescent biosensors and chemosensors available to report, profile and image PKs from the AGC, CMGC, CAMK, TK, and TKL kinases.
The segmented genome of Rotavirus alphagastroenteritidis facilitates the emergence of unusual reassortants, increasingly documented in the post-vaccine era. However, their long-term evolutionary dynamics and population-level persistence remain poorly understood. We investigated G1P[8] strains detected through hospital-based surveillance in northern and central Vietnam from 2012 to 2016. Electropherotyping, whole-genome sequencing, and phylogenetic analyses were performed to define genomic constellations and reconstruct evolutionary dynamics of DS-1-like reassortants. We documented four-year circulation patterns of DS-1-like G1P[8] strains, emerging in 2012/2013, peaking in mid-2014, and declining by 2016. Among 44 strains exhibiting short electropherotypes, at least three sequential genotype constellations (A-C) were identified: Constellation A likely arose in northern Vietnam through inter-genogroup reassortment between Wa-like G1P[8] (VP7/VP4) and DS-1-like G2P[4] strains; A related variant in central Vietnam suggested regional transmission from contemporaneous strains reported in Thailand and Japan; Constellation B involved acquisition of a Wa-like NSP2 gene; Constellation C included additional reassortment with bovine-like NSP2 and NSP4 genes from a co-circulating G8P[8] strain. No significant differences in clinical severity were observed between DS-1-like and Wa-like infections, and no cases of either genotype were detected among fully vaccinated children. Overall, this study describes a stepwise reassortment process involving intergenogroup, intragenogroup, and potential zoonotic events. Genomic diversification in this setting was not associated with increased virulence or evidence of immune escape. These findings highlight the need for continued genomic surveillance and broader sampling to better resolve the evolutionary dynamics of rotavirus reassortants.
A next-generation Mars Network is investigated to determine a configuration optimized for both communications and positioning performance for surface users. A previously proposed 6000 km altitude, 3-satellite equatorial constellation that was found to be optimal for communications to surface users located in the latitude range from 60°S to 60°N is shown to be deficient for surface positioning. Inclining the 3-satellite configuration between 30° and 50° improves positioning performance to users in this latitude range; however, due to a lack of coverage this improvement is primarily seen for positioning when using tracking data collected over long timespans. Moving to an inclined 6-satellite case and using a Walker 6/2/0 delta configuration, at selected inclinations and altitudes, greatly improves the positioning solution performance over shorter timescales, with the best performance obtained with orbits inclined at 50°. Also examined were continuous coverage global constellations that were compared to the Walker 50°: 6/2/0 configurations. The single fold continuous coverage Walker 55.7°:7/7/5 constellation slightly improves the positioning performance and provides more uniform and continuous coverage to the poles, which the Walker 50°:6/2/0 case cannot. Finally, a Walker 57.1°: 8/8/2 constellation that provides continuous twofold coverage was examined; however, the high altitude required for this case reduces its communication performance and yields poorer positioning performance relative to the Walker 55.7°:7/7/5. It is concluded that a next generation Mars Network with focused support to users between 60°S and 60°N that the Walker 50°: 6/2/0 is the best positioning and communications performance while, for continuous coverage global coverage, the Walker 55.7°: 7/7/5 is superior.
To further enhance the covert communication capability of satellite-ground-integrated sensor networks, a dual-polarization constellation joint modulation scheme based on frequency-hopping double-layer multi-parameter weighted fractional Fourier transform (FH-DL-MPWFRFT) is proposed from the perspective of physical layer security. The proposed scheme integrates the constellation confusion property of weighted fractional Fourier transform (WFRFT) with the anti-interception capability of frequency-hopping (FH) phase scrambling. Specifically, the weighted parameters of conventional 4-WFRFT are extended to construct a multi-parameter and multi-layer signal representation, and FH phase scrambling is introduced to realize dynamic constellation rotation and phase-domain encryption. Furthermore, a secure transmission model for satellite-ground-integrated sensor networks is established, revealing the constellation optimization principle and the fission-fusion mechanism of dual-polarization signals. Simulation results show that, compared with the non-FH benchmark, the proposed scheme significantly improves waveform-level anti-interception performance; even when eavesdropper obtains the modulation scheme and partial transform parameters, the symbol error rate (SER) of quadrature phase shift keying (QPSK) and four-phase modulation (4PM) signals remains around 0.4 to 0.5 under parameter mismatch, indicating that effective demodulation is difficult to achieve.
Retinitis pigmentosa (RP) is an inherited retinal disease (IRD), whereby each affected individual typically harbours pathogenic variants in a single causative gene, yet the disorder exhibits marked genetic heterogeneity, with more than 100 genes reported to underlie RP. Dual-gene defect constellations are rare but may modify disease presentation, complicating diagnosis, prognosis and therapeutic decision-making. This study aimed to characterize the clinical and genetic effects of dual-gene variants in patients with RP as the lead diagnosis. We retrospectively analysed 10 affected individuals and their parents from eight families with confirmed dual-genotype constellations in RP-associated genes. Ophthalmic evaluation included best-corrected visual acuity (BCVA), visual fields, multimodal imaging, electroretinography (ERG) and full-field stimulus threshold testing (FST). Genetic analyses comprised whole genome sequencing and targeted segregation studies; for the latter, long-read sequencing was used to clarify cis/trans variant configuration. Genes involved were CEP290, RCBTB1, ABCA4, PDE6A, CRB1, EYS, PRPH2, MYO7A, RS1, USH2A, MT-TL1, RHO and BEST1, in various genotype constellations. Phenotypes ranged from early-onset severe rod-cone dystrophy to late-onset mild RP, largely reflecting gene-specific effects (e.g. EYS > CRB1 > PRPH2) and their interactions. Long-read sequencing revealed ABCA4 variants in cis, explaining asymptomatic carriers and informing gene therapy eligibility. Functional retinal testing highlighted gene-specific patterns, including macular preservation in EYS-driven RP and Best disease-associated macular changes. Dual-gene variant constellations contribute to heterogeneous RP phenotypes. Integrating comprehensive genetic analysis with detailed clinical assessment is critical to define gene-specific contributions, inform prognosis, guide clinical management and determine eligibility for emerging gene-based therapies.
High-capacity inter-satellite laser communication links are essential for global coverage, remote sensing, and deep space missions, but face challenges from path loss, pointing errors, and limited aperture sizes that degrade performance at extended ranges and high data rates. This work reports simulative evaluation of an Inter-Satellite Laser Communication Transmission (Is-LCT) system with 160 Gb/s data rate. Orthogonal Frequency Division Multiplexing (OFDM), Polarization Division Multiplexing (PDM), and 32-level Quadrature Amplitude Modulation (32-QAM) techniques have been used to enhance the system baud rate, bandwidth efficiency and transmission rate of the system. Advanced signal processing techniques have been used to improve the performance of the proposed system. The proposed Is-LCT system is investigated for enhancing range, optical efficiency, aperture diameter, laser power, and pointing error using Error Vector Magnitude (EVM), Bit Error Rate (BER), and constellation as the metrics for performance evaluation. The obtained results demonstrate reliable 160 Gb/s data transmission at 7000 km Is-LCT range with BER[Formula: see text]3.8[Formula: see text], EVM[Formula: see text] 12%, and clear constellation of the received optical signal.
Rotavirus A (RVA) G3P[3] genotype is widely reported in dogs and less frequently in cats, with only sporadic human cases worldwide. All reported human infections have occurred in children, suggesting increased susceptibility likely linked to close contact with pets and age-related hygiene practices. The identification of a novel genotype constellation in Brazilian canine G3P[3] strains in 2017 prompted full-genotype characterization of the historical RVA/Human-wt/BRA/IAL-R451/2011/G3P[3] strain, previously sequenced only for VP7 and VP4, to define its genomic constellation and relatedness to canine strains. All 11 segments were analyzed by RT-PCR, sequencing and phylogenetics. The rare genotype-lineage constellation G3.III-P[3]-I2.XX-R3.II-C2.V-M3.II-A9-N2.XXIV-T3.II-E3.II-H6.I, shared with Brazilian canine strains, was identified, supporting a potential common origin. RVA/Human-wt/BRA/IAL-R451/2011/G3P[3] strain showed high genetic similarity (93.2-99%) with canine, feline and canine/feline-like human strains worldwide, with six genes (VP1, VP6 and NSP2-NSP5) closely related to Brazilian dog isolates (97.6-99%), indicating its canine origin. NSP2 clustered with strains from domestic (bovine), synanthropic (rat) and human hosts, while VP7 and VP4 were associated with wildlife (bat; raccoon dog) and environmental (sewage; river water) strains, supporting interhost reassortment and highlighting aquatic environments as reservoirs for interspecies transmission. Identification of new lineages (VP1, VP3 and NSP2) within the AU-1-like backbone reflects its underexplored diversity. This novel constellation likely circulated in dogs and may spill over to humans via close contact, reinforcing a One Health approach to understand RVA zoonotic risk, especially in hotspot regions like Brazil.
Erdheim-Chester Disease (ECD) constitutes a rare and clinically heterogeneous non-Langerhans cell histiocytosis, characterized by the systemic infiltration of tissues by foamy, lipid-laden histiocytes. These cells typically exhibit an immunophenotypic profile positive for CD68 and negative for CD1a. The disease's multifaceted presentation, which can span from isolated bone lesions to fulminant multi-organ failure, frequently results in considerable diagnostic delay. In this case-based review, we describe the case of a 58-year-old who presented with a primary complaint of exertional dyspnoea and fatigue. The initial diagnostic evaluation revealed a hemodynamically significant circumferential pericardial effusion and imaging findings suggestive of aortitis. Clinical presentation of ECD depends on the organs and tissues involved, and may range from bone pain to neurological symptoms, endocrine dysfunction, and cardiac involvement. Cardiovascular involvement occurs in at least 40% of ECD patients, although it is frequently underdiagnosed. Cardiac ECD is heterogeneous and may mimic many alternative aetiologies. The infiltration of the right atrioventricular sulcus, right atrial walls, or interatrial septum is one of the most typical cardiac manifestations of ECD. Recognition of pseudo-tumour intra-atrial mass, pericardial involvement, as well as the circumferential encasement of the entire aorta, the so-called coated aorta, are other frequent findings. Diagnosis often requires a multimodal approach, in particular when cardiac symptoms represent the onset of clinical manifestation of ECD. The combined use of computed tomography, fluorodeoxyglucose positron emission tomography, dedicated cardiac and abdominal magnetic resonance imaging, and X-ray of long bones can collectively reveal a constellation of findings diagnostic of ECD.
Heterotaxy syndrome-polysplenia variant (left isomerism) with dextrocardia is a rare constellation of laterality defects characterized by left-isomerism, multiple splenic nodules, and associated vascular and visceral anomalies. This report describes an adult Ethiopian woman who presented with nonspecific abdominal pain and was found to have imaging features diagnostic of heterotaxy (polysplenia variant). A 36-year-old Ethiopian female presented with a three-day history of mild to moderate, nonradiating anterior abdominal pain. Physical examination revealed the apical impulse on the right and mild left upper quadrant tenderness. Contrast-enhanced CT of the chest and abdomen demonstrated dextrocardia with the cardiac apex directed to the right, right-sided aortic arch, interrupted inferior vena cava with azygos continuation, bilobed lungs consistent with left isomerism, multiple splenic nodules clustered in the left upper quadrant (polysplenia), and a short pancreas. Routine laboratory tests were unremarkable. The final diagnosis was heterotaxy syndrome-polysplenia variant (left isomerism) with dextrocardia. The patient was managed conservatively for presumed costochondritis, counseled about her anatomical variation, advised to carry a medical alert card, and remained symptom-free at two-week follow-up. Imaging features in this patient are most consistent with heterotaxy syndrome (polysplenia variant) rather than isolated situs inversus totalis. Clear, consistent diagnostic terminology (heterotaxy-polysplenia variant with dextrocardia) is essential for accurate communication, appropriate counseling, and safe planning of future interventions. Recognition of such cases in underreported regions supports improved diagnostic awareness and tailored care.
AUTS2-related intellectual developmental disorder type 26 is a rare neurodevelopmental condition characterised by variable clinical manifestations, including developmental delay, dysmorphic features, and behavioural abnormalities, which may contribute to delayed diagnosis. We report the case of a two and a half years old boy born to consanguineous parents who presented with global developmental delay, poor weight gain, feeding difficulties, recurrent choking episodes, and multiple dysmorphic features. Physical examination demonstrated arched eyebrows, broad nasal bridge, upturned philtrum, strabismus, mild lower limb hypotonia, unilateral cryptorchidism, and hypospadias. Delayed motor and speech milestones with autistic features were also observed. The patient additionally had recurrent upper respiratory tract infections and adenotonsillar hypertrophy requiring adenotonsillectomy. Given the multisystem involvement and developmental concerns, a genetic disorder was suspected. Whole-exome sequencing identified a heterozygous pathogenic variant in the AUTS2 gene, confirming the diagnosis of intellectual developmental disorder, autosomal dominant 26 (MRD26). To our knowledge, this represents the first reported case of MRD26 from the Arabian Peninsula and the Gulf Cooperation Council region. This case highlights the importance of maintaining a high index of suspicion in children presenting with developmental delay and dysmorphic features. It also contributes to the AUTS2 syndrome phenotypic database by adding a patient from a previously under-represented ethnic and geographical background, by documenting an autosomal dominant variant identified within a consanguineous pedigree, and by drawing attention to a constellation of co-occurring hypospadias, unilateral cryptorchidism, and adenotonsillar hypertrophy requiring surgery, which appears infrequently reported in the existing AUTS2 literature. Early diagnosis may facilitate timely multidisciplinary management, appropriate developmental support, and family counselling.
In diabetic patients, hypoglycemia associated autonomic failure (HAAF) is a potentially lethal condition that results in attenuation of critical protective responses to low blood glucose, following repeated prior hypoglycemic episodes. The underlying mechanism(s) of HAAF is not fully understood. We previously demonstrated that activation of catecholamine (CA) neurons in the ventrolateral medulla (VLM) is both required and sufficient to elicit key protective responses to glucose deficit. Here we test the hypothesis that repeated selective activation of VLM CA neurons is sufficient to induce HAAF, even in the absence of glucose deficit. Using stereotaxic injections of an adeno-associated virus in female TH-Cre transgenic rats, we transfected rostral C1 CA neurons to express hM3D(Gq). In these rats, we found that a single clozapine-N-oxide (CNO) injection evoked robust hyperglycemia, with a magnitude and time course similar to those evoked by the glucoprivic agent, 2-deoxy-D-glucose (2DG). However, following repeated CNO injections in these same rats, the hyperglycemic response evoked by either CNO or 2DG were significantly attenuated. Moreover, plasma epinephrine levels, and Fos expression in VLM CA neurons and in the adrenal medulla, also were attenuated following repeated CNO injections. This constellation of effects is similar to those that define HAAF. Taken together our results suggest that repeated stimulation of VLM CA neurons mimics and could be a cause of the impairment of counterregulatory responses associated with pathogenesis of HAAF.
We propose an integrated transmission scheme for data center interconnects (DCIs) that jointly enables security and monitoring at the physical layer. A perception-embedded modulation (PEM) method is designed to embed device identifiers into modulated data, while channel anomalies are sensed based on the statistical characteristics of the constellation same-set ratio. To protect both the transmitted data and the embedded identifiers, chaotic noise injection is introduced, and reliable transmission of the masked signal is ensured through delta-sigma modulation (DSM). The proposed chaotic PEM-DSM encrypted signal at 64 GBaud is validated over a 240 km optical fiber link. The results demonstrate that the scheme achieves secure data transmission, accurately identifies unauthorized devices, and enables optical performance monitoring with a resolution of 1 dB.
Stercoral colitis (SC) is a life-threatening inflammatory condition caused by fecal impaction and chronic opioid-induced dysmotility. While classically presenting with abdominal pain, atypical presentation can lead to diagnostic delays and increased morbidity. A 72-year-old woman with chronic intranasal fentanyl use presented with localized rectal pain and overflow diarrhea. Initial imaging revealed SC but also identified cavitary pulmonary lesions and a hepatic mass. This constellation of findings initially raised high suspicion for disseminated malignancy. However, biopsy demonstrated inflammatory infiltrates consistent with hepatic abscess formation, raising concern for possible bacterial translocation from compromised colonic mucosa, although a definitive causal relationship could not be established. The patient was successfully managed with aggressive manual disimpaction and broad-spectrum antibiotics. This case illustrates the diagnostic complexity of SC, where concurrent systemic inflammatory findings may mimic metastatic disease and broaden the differential diagnosis considerably. It underscores the importance of considering possible gastrointestinal sources of systemic inflammation or infection in patients with severe SC and multiorgan inflammatory findings. Recognizing overflow diarrhea is critical to avoid inappropriate anti-motility therapy, which carries a high risk of colonic perforation in the setting of SC. Early cross-sectional imaging and prioritization of reversible causes are essential when managing such complex, multisystem presentations.
Prediabetes is a common metabolic condition affecting a substantial proportion of adults worldwide; however, most individuals remain undiagnosed owing to the prolonged asymptomatic phase of this condition. The oral cavity generates a constellation of clinically detectable changes during this intermediate glycemic stage, including periodontal attachment loss, salivary dysfunction, and oral microbiome dysbiosis, all of which can be examined by dental professionals. Periodontal clinical attachment loss and elevated glycated hemoglobin (HbA1c) levels show a dose-dependent relationship in nondiabetic populations, and active matrix metalloproteinase-8 (aMMP-8) in oral fluids correlates independently with prediabetes, even in its early stages. Salivary oxidative stress markers, adipokines, cariogenic bacterial loads, and physicochemical parameters are measurably altered before overt hyperglycemia is established. Oral microbial communities show reduced species richness, altered IgA immune responses, and shifts in keystone taxa in prediabetic individuals compared to those in healthy individuals. Chairside HbA1c measurement, aMMP-8 point-of-care testing, and structured interprofessional referral models have demonstrated high diagnostic yields in real-world dental settings. This narrative review explores the current literature and proposes dental practice as a first-line venue for opportunistic prediabetes detection, with an emphasis on actionable clinical strategies for practicing dentists.
Hereditary α-tryptasemia (HαT) is a common autosomal-dominant trait caused by additional copies of the gene TPSAB1 encoding for α-tryptase. This inheritance is the most common etiology for elevated basal serum tryptase (BST), occurring almost exclusively at BST ≥ 8 μg/L. In systemic mastocytosis (SM) and nonclonal mast cell-mediated disorders, HαT is linked to a complex constellation of symptoms. We sought to delineate the spectrum and burden of extended manifestations observed in patients with and without HαT presenting to an allergy department. A total of 332 allergy patients with BST ≥ 8 μg/L were prospectively enrolled. Blood was tested for HαT and KIT D816V mutation (to identify patients with SM) by digital droplet PCR. Symptom assessment was conducted with a HαT-customized questionnaire (n = 256). HαT-positive patients reported a significantly higher symptom burden than HαT-negative patients (9.3 vs 6.5; P < .001), particularly those referred for urticaria/angioedema (8.9 vs 5.5; P = .023) and atopic diseases (8.3 vs 4.2; P = .016). In allergy patients with HαT, symptom spectrum was extended to fatigue (+26%; P < .001), sleep disturbances (+13%; P = .049), and neuropsychiatric symptoms such as concentration issues (+26%; P < .001), memory impairment (+16%; P = .020), sadness/lack of motivation (+22%; P = .004), headaches (+19%; P = .006), abdominal pain (+21%; P = .002), and cardiovascular symptoms such as dizziness (+14%; P = .052), palpitations (+15%; P = .039), and orthostatic dysregulation (+22%; P = .002). HαT may have a broader clinical impact beyond classic allergy-immunology connections and may be associated with extended clinical phenotypes. This suggests an integrative approach to medical practice in allergy patients.
Background: Lateral cephalometric radiographs and large-field cone-beam computed tomography (CBCT) routinely used in orthodontics and maxillofacial radiology can reveal incidental pituitary tumors in the sellar region. Given the regular use of these imaging modalities, a structured overview of how pituitary tumors present on dental radiographs and how often they occur is clinically relevant. Methods: A scoping review was conducted according to PRISMA-ScR. MEDLINE via PubMed, Livivo, and Google Scholar were searched up to 20 January 2026 using MeSH terms and keywords for pituitary tumors and dental radiology. Human studies in English or German reporting on radiological presentation, clinical manifestation and epidemiology of pituitary tumors in the context of dental imaging were included. Study selection was performed independently by two reviewers. Results: Of 150 records, 15 studies were included: 2 case-control studies, 5 observational studies, 6 case reports, 1 questionnaire-based study and 1 neurosurgical guideline. Pituitary tumors most frequently presented with enlargement, deformation, or double contour of the sella turcica; growth hormone-producing adenomas additionally showed cephalometric changes such as mandibular and frontal sinus enlargement. The evidence is largely descriptive and does not permit robust estimates of prevalence or diagnostic accuracy but consistently identifies radiological "red flags" and recurrent clinical constellations, especially in acromegaly or unexplained craniofacial changes. Conclusions: Pituitary tumors, among the most common brain tumors, may first be suspected on routine dental radiographs. Distinct radiographic abnormalities combined with suggestive clinical features should prompt timely endocrine and neuroradiological evaluation, underscoring the need for heightened awareness among dental professionals.
A 4-year-old spayed female mixed breed dog presented for chronic upper airway noises and dysphagia. The dog presented for inspiratory stridor and expiratory stertor. Serum creatine kinase activity was 3,296 IU/L, and cholesterol and triglyceride levels were elevated at 353 mg/dL and 201 mg/dL, respectively. In-house thyroxine levels were below the reference range, prompting the submission of a comprehensive thyroid profile to an outside reference laboratory. Head and cervical CT with contrast showed perivertebral/perilaryngeal muscle thickening and contrast enhancement. Electrodiagnostics of the pelvic limbs and head showed diffuse spontaneous activity with normal motor nerve conduction velocity. Muscle biopsies revealed an inflammatory myopathy in both masticatory muscles and pelvic limb muscles. The serum 2M antibody titer was positive. Comprehensive infectious PCR and serology testing were negative. The constellation of findings is compatible with an overlap syndrome of masticatory myositis and immune-mediated polymyositis. A comprehensive thyroid panel consisting of total thyroxine, total triiodothyronine, free thyroxine by dialysis, T4 and T3 autoantibodies, thyroid-stimulating hormone, and thyroglobulin autoantibodies later returned supported results for lymphocytic thyroiditis. Treatment with immunosuppressive doses of prednisone was effective in reducing, but not eliminating, the respiratory noises and dysphagia, with improved quality of life 763 days after initial presentation. This is a clinical description of an overlap syndrome of masticatory myositis and polymyositis, further complicated by lymphocytic thyroiditis. This case report highlights the importance of differentiating euthyroid sick syndrome and lymphocytic thyroiditis in dogs with chronic immune-mediated illness.
Although more than 60 psychotropic drugs are currently approved for mental illness, their therapeutic index remains modest, with limited efficacy over placebo and substantial adverse effects. Initial concerns that glucagon-like peptide-1 (GLP-1) analogs might produce starvation-related central nervous system (CNS) effects, like those of anorexia nervosa, have been subverted by their largely positive outcomes. Clinical observations of reduced "food noise", altered reward behaviors, and improved mood have prompted trials evaluating these agents for their potential as psychotropics. This serendipitous paradox compels re-evaluation of prevailing psychiatric disease models. The focus on small-molecule neurotransmitters operating at synapses appears insufficient to explain complex psychiatric illness or the effects of larger molecules like GLP-1. Notably, psychiatric disorders, though familial, do not follow Mendelian inheritance and show considerable heterogeneity in symptoms, suggesting that DNA sequence variation alone is inadequate as a unifying explanation. Alan Turing's pre-DNA morphogenesis model, emphasizing chemical gradients and developmental divergence, offers an alternative framework. While Virchow and Cajal established neuron-centered paradigms, later reinforced by neurochemical and monoaminergic discoveries, emerging evidence increasingly implicates neuroglia, particularly astrocytes, in higher mental functions, and their disruption in psychiatric diseases. This nascent and fragmented field warrants integration. Herein, we review astrocyte phylogenetics across vertebrates, their regional specialization within the human brain, and their synthesis of diverse small and large molecules. We propose adopting a model in which neurons and neuroglia act together in syncytial constellations that underlie complex mental functions, mediated by their molecular products. Finally, we outline strategies for drug-development and therapeutics harnessing syncytial constellations and astrocyte-derived molecules.
(Likely) pathogenic variants (pVs) in hereditary breast and/or ovarian cancer (HBOC) genes increase cancer risk, but the clinical implications of multiple pVs remain insufficiently understood. Using data from the prospective nationwide German Consortium for HBOC registry, we conducted a case-control study of genotype-phenotype associations, matching female carriers to compare cancer risk and disease severity between multiple and single heterozygous (SH) pV carriers. Among 26,983 carriers of single or multiple HBOC-associated pVs, 409 individuals had multiple heterozygosities, including 400 double heterozygous (DH) carriers. In a subcohort tested for 13 core genes, 98/3407 (2.9%) individuals had multiple HBOC-associated pVs. Breast cancers (BCs) in DH women with pVs in BRCA1 and another gene were predominantly triple-negative, even when the second, non-BRCA1 pV was typically associated with hormone receptor (HR)-positive BC. By contrast, BRCA1/CHEK2 DH carriers showed more HR-positive BCs than BRCA1 SH women. The median age at first BC was similar in female ATM/CHEK2 DH carriers and BRCA1 SH carriers (41.5 [IQR 14.0] vs. 41.3 [14.1] years). Matched BRCA1 and BRCA2 SH carriers were less likely to present with higher disease severity than BRCA1/BRCA2 DH carriers (BRCA1: OR 0.396 [0.180-0.87]; BRCA2: OR 0.224 [0.100-0.50]). Multiple heterozygosity in HBOC core genes is more frequent than previously assumed. Our data indicate that gene-gene constellations can reshape tumour phenotype and clinical severity rather than following single-gene expectations. Integrating multiple pVs into risk assessment and counselling may enhance personalised surveillance and risk-reducing strategies for DH individuals and their families in the era of widespread multigene testing.