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1.
Int J Legal Med ; 138(4): 1369-1376, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38374287

RESUMO

Both hyper- and hypothermia are problematic in temperature based forensic time since death estimation. Hyperthermia may occur in infection, traumatic brain injury, and intoxication. Hypothermia is encountered predominantly in exposure. Sepsis may present itself clinically as hypothermic. Sepsis is not uncommon in the forensic setting and mostly occurs in the context of malpractice accusations. There is usually little overlap between sepsis and typical forensic time since death estimation scenarios of violent or otherwise suspicious deaths. In the presented case, hypothermia and time since death estimations did collide. An inmate was found dead in his jail cell. Wardens claimed they had visually approached him alive relatively shortly prior. Rectal temperature measurements, using two separate crime scene thermometers as well as temperature loggers, revealed low rectal temperature at relatively high ambient temperature. These findings suggested a much longer postmortem interval and consequently raised doubts about the stated timeline. The wardens' claims were however confirmed by camera recordings, which also allowed a reasonable estimate of the true time of death. The cause of death was confirmed as septic organ failure at autopsy, which explained low rectal temperature. The presence of WISCHNEWSKI-spots was noted. When the PRISM-method was applied to the temperature recordings, low rectal temperature at the time of death was detected successfully. However, adaptation of the underlying equation for lower "starting temperature" did not produce satisfactory results. It is concluded that even though hypothermia at the time of death may possibly be detected from temperature data, attempts at time since death estimation for cases of hypothermia by adaptation of the equation should be avoided.


Assuntos
Temperatura Corporal , Hipotermia , Sepse , Humanos , Masculino , Mudanças Depois da Morte , Adulto
2.
Photochem Photobiol Sci ; 23(8): 1485-1494, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38935211

RESUMO

In this work the influence of o-fluorine substituents on the photo-dehydro-Diels-Alder (PDDA) reaction was investigated and the findings of this study were applied to the total synthesis of natural products. The reactant molecules consisted of two alkyl arylpropiolates, connected by a suberic acid tether and bearing fluorine substituents in each of the o-positions. While quantum chemical calculations suggested that a fluorine substituent prevents an attack of the adjacent carbon atom in the second C-C bond forming step of the PDDA reaction, this attack took place nevertheless. The subsequent fluoride elimination, assisted by protic solvents or trialkylsilanes, resulted in an "Umpolung" of the 4-position of the cycloallene intermediate enabling the introduction of nucleophiles at this position. The nucleophilic replacement of the second fluorine substituent could also be triggered photochemically. After removal of the tether, the two arene moieties stand nearly perpendicular to each other and a selective excitation of the naphthalene moiety was possible. This led to an intramolecular photoinduced electron transfer (PET) followed by a nucleophilic replacement of the fluoride according to a SR+N1Ar* mechanism. The formed phenolic hydroxyl group underwent spontaneous lactonization with the adjacent ester group. Based on these results, the first total synthesis of the lignan Comfreyn A and some structural analogues were developed.

3.
Inorg Chem ; 63(2): 1480-1487, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38154029

RESUMO

In this work, we present the synthesis, characterization, and optical properties of Sr5Si7P2N16:Eu2+, the first tetrahedral (Si,P)-N network in which Si occupies more than 50% of the tetrahedra. While past studies have shown progress with anionic (Si,P)-N networks, the potential of silicon-rich compounds remains untapped. The synthesized compound Sr5Si7P2N16 exhibits a unique mixture of substitutional order and positional disorder within its network. The analytical challenges posed by the similarities between Si4+ and P5+, along with the network's disorder, were overcome by combining single-crystal X-ray diffraction and scanning transmission electron microscopy EDX mapping. Low-cost crystallographic calculations provided additional insights into the identification of tetrahedral occupations in mixed networks. Luminescence investigations on Sr5Si7P2N16:Eu2+ revealed yellow emission, adding to the known blue, green, and orange emission maxima of Sr-(Si,P)-N networks, highlighting the variability of such compounds.

4.
Phys Chem Chem Phys ; 26(7): 6277-6291, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38305760

RESUMO

We have previously presented a computational protocol that is based on an embedded cluster model and operates in the framework of TD-DFT in conjunction with the excited state dynamics (ESD) approach. The protocol is able to predict the experimental absorption and emission spectral shapes of Eu2+-doped phosphors. In this work, the applicability domain of the above protocol is expanded to Eu2+-doped phosphors bearing multiple candidate Eu doping centers. It will be demonstrated that this protocol provides full control of the parameter space that describes the emission process. The stability of Eu doping at various centers is explored through local energy decomposition (LED) analysis of DLPNO-CCSD(T) energies. This enables further development of the understanding of the electronic structure of the targeted phosphors, the diverse interactions between Eu and the local environment, and their impact on Eu doping probability, and control of the emission properties. Hence, it can be employed to systematically improve deficiencies of existing phosphor materials, defined by the presence of various intensity emission bands at undesired frequencies, towards classes of candidate Eu2+-doped phosphors with desired narrow band red emission. For this purpose, the chosen study set consists of three UCr4C4-based narrow-band phosphors, namely the known alkali lithosilicates RbNa[Li3SiO4]2:Eu2+ (RNLSO2), RbNa3[Li3SiO4]4:Eu2+ (RNLSO) and their isotypic nitridolithoaluminate phosphors consisting of CaBa[LiAl3N4]2:Eu2+ (CBLA2) and the proposed Ca3Ba[LiAl3N4]4:Eu2+ (CBLA), respectively. The theoretical analysis presented in this work led us to propose a modification of the CBLA2 phosphor that should have improved and unprecedented narrow band red emission properties. Finally, we believe that the analysis presented here is important for the future rational design of novel Eu2+-doped phosphor materials, with a wide range of applications in science and technology.

5.
Arch Toxicol ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38955864

RESUMO

Many fatal intoxications have been reported in connection with the consumption of newer, highly potent synthetic cannabinoids. Yet, a possible postmortem redistribution (PMR) might complicate reliable interpretation of analytical results. Thus, it is necessary to investigate the PMR-potential of new synthetic cannabinoids. The pig model has already proven to be suitable for this purpose. Hence, the aim of this study was to study the PMR of the synthetic cannabinoid 5F-MDMB-P7AICA and its main metabolite 5F-MDMB-P7AICA-dimethylbutanoic acid (DBA). 5F-MDMB-P7AICA (200 µg/kg body weight) was administered by inhalation to anesthetized and ventilated pigs. At the end of the experiment, the animals were euthanized and stored at room temperature for 3 days. Tissue and body fluid samples were taken daily. Specimens were analyzed after solid phase extraction using a standard addition method and LC-MS/MS, blood was quantified after protein precipitation using a validated method. In perimortem samples, 5F-MDMB-P7AICA was found mainly in adipose tissue, bile fluid, and duodenum contents. Small amounts of 5F-MDMB-P7AICA were found in blood, muscle, brain, liver, and lung. High concentrations of DBA were found primarily in bile fluid, duodenum contents, urine, and kidney/perirenal fat tissue. In the remaining tissues, rather low amounts could be found. In comparison to older synthetic cannabinoids, PMR of 5F-MDMB-P7AICA was less pronounced. Concentrations in blood also appear to remain relatively stable at a low level postmortem. Muscle, kidney, fat, and duodenum content are suitable alternative matrices for the detection of 5F-MDMB-P7AICA and DBA, if blood specimens are not available. In conclusion, concentrations of 5F-MDMB-P7AICA and its main metabolite DBA are not relevantly affected by PMR.

6.
Gesundheitswesen ; 86(5): 380-388, 2024 May.
Artigo em Alemão | MEDLINE | ID: mdl-38134915

RESUMO

BACKGROUND: The aim of this study was to investigate the experiences, barriers, and solutions in communication during the provision of care for people with intellectual developmental disabilities in Germany. As there are approximately 350,000 people living with intellectual or developmental disabilities in Germany, who rely on assistance when communicating with healthcare providers, this study was conducted to examine the communication challenges and potential solutions in this population. The analysis especially focused on the potentials of digital applications facilitating information transfer. METHODS: Thirteen expert interviews were conducted using a structured interview guide with caregivers and medical providers to people with intellectual developmental disabilities. The interviews were analyzed using an inductive and deductive content analysis approach, according to Meuser and Nagel. RESULTS: The results revealed that the provision of care for people with intellectual developmental disabilities was characterized by time constraints and uncertainty when caregivers lack experience in caring for this population. Additionally, information transfer increased in complexity due to an overload of individual information provided by caregivers verbally or paper-based as well due to the passive role of patients who were usually not actively involved in the communication process. With regard to the potential for integrating digital applications for information transfer, a controversy between opportunity and risk emerged. CONCLUSION: The findings demonstrate that there is a need to implement training programs for professionals to enable them to offer improved health care for people with intellectual developmental disabilities. It is essential that caregivers are given sufficient time to communicate with patients, and that digital applications are utilized to support information transfer. Moreover, other research shows that digital applications offer new possibilities to communicate with people with intellectual developmental disabilities, such as the use of simplified or pictorial language. By addressing these communication challenges, healthcare professionals may be able to provide more effective and efficient care to this population. However, this requires further research, which addresses the controversial results regarding digital applications outlined in this paper.


Assuntos
Deficiência Intelectual , Humanos , Deficiência Intelectual/terapia , Deficiência Intelectual/psicologia , Alemanha , Feminino , Adulto , Masculino , Cuidadores/psicologia , Pessoa de Meia-Idade , Comunicação
7.
BMC Oral Health ; 24(1): 345, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38500122

RESUMO

BACKGROUND: Finding and registering the maxillary-mandibular jaw relation is crucial in dental practice. Several comparative studies have been conducted to investigate the reproducibility and accuracy of techniques for determining the centric relation (CR) position of the mandible. The aim of our study was to determine which of seven different CR determination methods had the smallest deviation from the theoretical zero with the help of a digital mandibular motion analyser. The chosen theoretical zero position, the maximal intercuspal position (MIP), is the most reproducible and widely used position. METHODS: Thirty-four volunteers (24 females and 10 males) with a mean (SD) age of 29.1 (± 7.3) years with a negative history of temporomandibular disorder (TMD) participated in the study. A digital mandibular motion analyser was used to register the condylar position after the use of each technique for the determination of CR. The calibration was performed to the maximal intercuspal position (MIP) for each volunteer. The investigated techniques were (A) the gothic arch tracer, (B) the adduction field method, (C) Dawson's bimanual manipulation, (D) the patient placing the tongue tip on the palatal rugae, (E) the patient placing the tongue tip to the border of the hard and soft palate, (F) the patient actively pulling the chin backwards, and (G) the examiner pushing the patient's chin back. RESULTS: The position of the mandibular condyle was illustrated in a three-dimensional coordinate system, where the origin represented the MIP. Among the seven methods examined, five showed significant deviations compared to the MIP. Among these, two methods resulted in posterior deviation of the condyles. Methods C and E coincided with the MIP in all directions. CONCLUSIONS: Within the limitations of our study, we found that the smallest deviations from our theoretical zero (MIP) among the investigated centric relation determining methods were obtained with the bimanual mandibular manipulation technique derived from Dawson and the placement of the tongue tip on the border of the hard and soft palate (linguomandibular homotrophy theory).


Assuntos
Mandíbula , Côndilo Mandibular , Masculino , Feminino , Humanos , Adulto Jovem , Adulto , Relação Central , Reprodutibilidade dos Testes , Queixo , Registro da Relação Maxilomandibular
8.
Angew Chem Int Ed Engl ; 63(17): e202401419, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38340088

RESUMO

This study presents the synthesis and characterization of oxonitridosilicate phosphates Sr3SiP3O2N7, Sr5Si2P4ON12, and Sr16Si9P9O7N33 as the first of their kind. These compounds were synthesized under high-temperature (1400 °C) and high-pressure (3 GPa) conditions. A unique structural feature is their common fundamental building unit, a vierer single chain of (Si, P)(O, N)4 tetrahedra. All tetrahedra comprise substitutional disorder which is why we refer to it as the fundamental disorder unit (FDU). We classified four different FDU motifs, revealing systematic bonding patterns. Including literature known Sr5Si2P6N16, three of the four patterns were found in the presented compounds. Common techniques like single-crystal X-ray diffraction (SCXRD), elemental analyses, and 31P nuclear magnetic resonance (NMR) spectroscopy were utilized for structural analysis. Additionally, low-cost crystallographic calculations (LCC) provided insights into the structure of Sr16Si9P9O7N33 where NMR data were unavailable due to the lack of bulk samples. The optical properties of these compounds, when doped with Eu2+, were investigated using photoluminescence excitation (PLE), photoluminescence (PL) measurements, and density functional theory (DFT) calculations. Factors influencing the emission properties, including thermal quenching mechanisms, were discussed. This research reveals the new class of oxonitridosilicate phosphates with unique systematic structural features that offer potential for theoretical studies of luminescence and band gap tuning in insulators.

9.
Angew Chem Int Ed Engl ; 63(23): e202403648, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38567876

RESUMO

Tetrahedron-based nitrides offer a wide range of properties and applications. Highly condensed nitridophosphates are examples of nitrides that exhibit fascinating luminescence properties when doped with Eu2+, making them appealing for industrial applications. Here, we present the first nitridomagnesophosphate solid solution series Ba3-xSrx[Mg2P10N20] : Eu2+ (x=0-3), synthesized by a high-pressure high-temperature approach using the multianvil technique (3 GPa, 1400 °C). Starting from the binary nitrides P3N5 and Mg3N2 and the respective alkaline earth azides, we incorporate Mg into the P/N framework to increase the degree of condensation κ to 0.6, the highest observed value for alkaline earth nitridophosphates. The crystal structure was elucidated by single-crystal X-ray diffraction, powder X-ray diffraction, energy-dispersive X-ray spectroscopy (EDX), and solid-state NMR. DFT calculations were performed on the title compounds and other related highly condensed nitridophosphates to investigate the influence of Mg in the P/N network. Eu2+-doped samples of the solid solution series show a tunable narrow-band emission from cyan to green (492-515 nm), which is attributed to the preferred doping of a single crystallographic site. Experimental confirmation of this assumption was provided by overdoping experiments and STEM-HAADF studies on the series as well on the stoichiometric compound Ba2Eu[Mg2P10N20] with additional atomic resolution energy-dispersive X-ray spectroscopy (EDX) mapping.

10.
Artigo em Inglês | MEDLINE | ID: mdl-38147109

RESUMO

Animal-assisted therapy (AAT) is becoming increasingly popular. The possibilities and guidelines for interventions and methods are very diverse. Currently, published studies mainly concentrate on effects in paediatrics, outpatient therapy and schools. Specific recommendations for AAT in the context of inpatient child and adolescent psychiatry do not exist. This systematic review will attempt to evaluate the existing studies in terms of their methodological quality and specify positive and negative effects, aiming to provide a decision-making aid for everyday clinical practice. A systematic literature search (PubMed/MEDLINE, APA PsycINFO, PubPsych, ProQuest, Google Scholar, and Cochrane Library) according to the PRISMA criteria resulted in 1,908 identified hits, of which 49 articles were reviewed in full text. Three raters contributed to the review of the articles using a criteria-guided codebook. This systematic review is listed in the PROSPERO database (CRD42022358909). Quality analysis was conducted using Effective Public Health Practice Project (EPHPP). Five studies were identified. The majority of these showed deficits in quality. Therapeutic effects and positive influences on the psychopathological status, interpersonal relationships and subjective well-being or attitudes towards canine-assisted therapy (CAT) could be identified. Current studies indicate positive therapeutic effects of CAT in the inpatient treatment of children and adolescents. A cautiously positive perspective is warranted, but a general recommendation for CAT cannot be given. CAT should be carefully considered, planned, and implemented by professionals. For the future, further randomised controlled studies including follow-up studies, larger subject groups and clinically evaluated interventions are necessary to validate the current results.

11.
Children (Basel) ; 11(3)2024 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-38539390

RESUMO

BACKGROUND: The current literature lacks scientific research on child and adolescent psychiatrists' (CAPPS) perspectives on dental and oral health. This study aims to investigate the opinions and approaches of child and adolescent psychiatrists and their patients regarding oral and dental health. METHODS: A questionnaire-based cross-sectional study was conducted among members of the Professional Association for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy in Germany. RESULTS: Out of the association members, 10.9% (n = 109) participated, with 5.2% (n = 52; 38f/14m) completing the questionnaire. Dental and oral health topics were discussed with one-fifth of the patients (19.2%), while 11.5% reported that they were "never" a part of their therapy. Patient-related concerns about dental and oral health were primarily brought into the context of child and adolescent psychiatric work. Dental treatment anxieties were prominent. Only 3.8% of the participants regularly assigned diagnoses related to dental status. The CAPPS employ a bio-psycho-social model for the genesis of oral health-related conditions in Children and Adolescents with Special Needs. CONCLUSIONS: CAPPS have a foundation in relationship-based work for assessing oral and dental healthcare and providing recommendations for further dental care. Regional networking and science must be further developed.

12.
BDJ Open ; 10(1): 32, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637510

RESUMO

OBJECTIVE: In the temporomandibular joint two separate movements of rotation and translation occur in two articular spaces during mouth opening. Over the years, the approach has changed considerably, but it is still subject to controversy as to which of these movement is involved in the initial stage of mouth opening. In the present study, the extent of rotation and translation was investigated in the first 5 mm of mouth opening. MATERIALS AND METHODS: The study was carried out on 46 volunteers. Anamnesis was taken and patients were examined. For the investigation, an ultrasonic digital motion analyser (KaVo Arcus Digma 2) was applied. The measurements were made after calibration to an arbitrary axis. Each participant performed three open-close movements in succession, starting from maximum intercuspal position. RESULTS: Data were statistically processed using cubic spline interpolation. Linear regression was then used. The resulting line is significantly (p < 0.0001) different from the horizontal that represents only rotational movement. CONCLUSION: The results show that during mouth opening from maximum intercuspal position, translation is present continuously in addition to rotation. Therefore, it might be time to re-evaluate the principle of a pure rotational approach.

13.
Front Immunol ; 15: 1386160, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38779658

RESUMO

The study of peptide repertoires presented by major histocompatibility complex (MHC) molecules and the identification of potential T-cell epitopes contribute to a multitude of immunopeptidome-based treatment approaches. Epitope mapping is essential for the development of promising epitope-based approaches in vaccination as well as for innovative therapeutics for autoimmune diseases, infectious diseases, and cancer. It also plays a critical role in the immunogenicity assessment of protein therapeutics with regard to safety and efficacy concerns. The main challenge emerges from the highly polymorphic nature of the human leukocyte antigen (HLA) molecules leading to the requirement of a peptide mapping strategy for a single HLA allele. As many autoimmune diseases are linked to at least one specific antigen, we established FASTMAP, an innovative strategy to transiently co-transfect a single HLA allele combined with a disease-specific antigen into a human cell line. This approach allows the specific identification of HLA-bound peptides using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Using FASTMAP, we found a comparable spectrum of endogenous peptides presented by the most frequently expressed HLA alleles in the world's population compared to what has been described in literature. To ensure a reliable peptide mapping workflow, we combined the HLA alleles with well-known human model antigens like coagulation factor VIII, acetylcholine receptor subunit alpha, protein structures of the SARS-CoV-2 virus, and myelin basic protein. Using these model antigens, we have been able to identify a broad range of peptides that are in line with already published and in silico predicted T-cell epitopes of the specific HLA/model antigen combination. The transient co-expression of a single affinity-tagged MHC molecule combined with a disease-specific antigen in a human cell line in our FASTMAP pipeline provides the opportunity to identify potential T-cell epitopes/endogenously processed MHC-bound peptides in a very cost-effective, fast, and customizable system with high-throughput potential.


Assuntos
Mapeamento de Epitopos , Epitopos de Linfócito T , Antígenos HLA-E , Proteômica , Proteômica/métodos , Antígenos HLA-E/análise , Epitopos de Linfócito T/análise , Mapeamento de Epitopos/métodos , Mapeamento de Epitopos/normas , Doenças Autoimunes/diagnóstico , Doenças Autoimunes/imunologia , Linhagem Celular , Humanos , Espectrometria de Massa com Cromatografia Líquida , Peptídeos/isolamento & purificação , Células Apresentadoras de Antígenos/imunologia , Células Artificiais/imunologia
14.
bioRxiv ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38979150

RESUMO

The menopausal transition (MT) is associated with an increased risk for many disorders including neurological and mental disorders. Brain imaging studies in living humans show changes in brain metabolism and structure that may contribute to the MT-associated brain disease risk. Although deficits in ovarian hormones have been implicated, cellular and molecular studies of the brain undergoing MT are currently lacking, mostly due to a difficulty in studying MT in postmortem human brain. To enable this research, we explored 39 candidate biomarkers for menopausal status in 42 pre-, peri-, and post-menopausal subjects across three postmortem tissues: blood, the hypothalamus, and pituitary gland. We identified thirteen significant and seven strongest menopausal biomarkers across the three tissues. Using these biomarkers, we generated multi-tissue and tissue-specific composite measures that allow the postmortem identification of the menopausal status across different age ranges, including the "perimenopausal", 45-55-year-old group. Our findings enable the study of cellular and molecular mechanisms underlying increased neuropsychiatric risk during the MT, opening the path for hormone status-informed, precision medicine approach in women's mental health.

15.
Head Face Med ; 20(1): 36, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877506

RESUMO

INTRODUCTION: Amelogenesis imperfecta (AI) is a genetically determined, non-syndromic enamel dysplasia that may manifest as hypoplasia, hypomaturation, or hypocalcification and can commonly be classified into four primary groups. In this retrospective analysis, specific orofacial characteristics are described and associated with each of the AI types based on a patient cohort from Witten/Herdecke University, Germany. METHODS: Data from 19 patients (ten male and nine female, mean age 12.27 ± 4.06 years) with AI who presented at the Department of Orthodontics between July 2011 and December 2023 were analyzed. Baseline skeletal and dental conditions were assessed, including the presence of hypodontia, displacements, and taurodontism. AI was classified into classes I-IV based on phenotype. Treatment needs were evaluated according to the main findings following the German KIG classification, while the radiological enamel situation was determined using panoramic radiographs. RESULTS: An approximately equal distribution between classes II and III was found and a slight inclination toward a dolichofacial configuration (ΔML-NSL: 5.07 ± 9.23°, ΔML-NL: 4.24 ± 8.04°). Regarding orthodontic findings, disturbance in tooth eruption as well as open bite were the most prevalent issues (both 36.8%, n = 7). The most common AI classes were type I and II, which show an almost even distribution about the skeletal classes in sagittal dimension, while dolichofacial configuration was found most frequently in vertical dimension. CONCLUSION: Both clinical and radiological orthodontic findings in context with AI are subject to extensive distribution. It seems that no specific orofacial findings can be confirmed in association with AI with regard to the common simple classes I-IV. It may be more appropriate to differentiate the many subtypes according to their genetic aspects to identify possible associated orthodontic findings.


Assuntos
Amelogênese Imperfeita , Humanos , Amelogênese Imperfeita/terapia , Amelogênese Imperfeita/genética , Masculino , Feminino , Estudos Retrospectivos , Criança , Adolescente , Alemanha , Radiografia Panorâmica , Ortodontia Corretiva/métodos , Má Oclusão/terapia
16.
iScience ; 27(3): 109113, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38375233

RESUMO

Pubertal timing, including age at menarche (AAM), is a heritable trait linked to lifetime health outcomes. Here, we investigate genetic mechanisms underlying AAM by combining genome-wide association study (GWAS) data with investigations of two rare genetic conditions clinically associated with altered AAM: Williams syndrome (WS), a 7q11.23 hemideletion characterized by early puberty; and duplication of the same genes (7q11.23 Duplication syndrome [Dup7]) characterized by delayed puberty. First, we confirm that AAM-derived polygenic scores in typically developing children (TD) explain a modest amount of variance in AAM (R2 = 0.09; p = 0.04). Next, we demonstrate that 7q11.23 copy number impacts AAM (WS < TD < Dup7; p = 1.2x10-8, η2 = 0.45) and pituitary volume (WS < TD < Dup7; p = 3x10-5, ηp2 = 0.2) with greater effect sizes. Finally, we relate an AAM-GWAS signal in 7q11.23 to altered expression in postmortem brains of STAG3L2 (p = 1.7x10-17), a gene we also find differentially expressed with 7q11.23 copy number (p = 0.03). Collectively, these data explicate the role of 7q11.23 in pubertal onset, with STAG3L2 and pituitary development as potential mediators.

17.
J Clin Med ; 13(10)2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38792540

RESUMO

Background: This is a retrospective longitudinal study comparing 374 patients with Parkinson's disease (PD) who were treated in centers offering a specialized program of enhanced rehabilitation therapy in addition to expert outpatient care to 387 patients with PD, who only received expert outpatient care at movement disorders centers in Italy. Methods: The data are from subjects recruited in the Parkinson's Outcome Project (POP) at six Italian centers that are part of a multicenter collaboration for care quality improvement (the Fresco Network). The effects were measured with a baseline and a follow-up clinical evaluation of the Timed-Up-and-Go test (TUG), Parkinson's Disease Questionnaire (PDQ-39), and Multidimensional Caregiver Strain Index (MCSI), the number of falls and hospitalizations for any cause. We used a generalized linear mixed model with the dependent variables being the response variable, which included the covariates demographics, evaluation, and treatment variables. Results: We found that the subjects who underwent specialized enhanced rehabilitation had a better motor outcome over time than those who were managed by expert neurologists but had participated in community programs for exercise and other allied health interventions. The greatest effects were seen in patients in the early stages of the disease with a high amount of vigorous exercise per week in the last six months. Similar effects were seen for PDQ39, MCSI, the number of falls, and hospitalization. Conclusions: Long-term benefits to motor function and the quality of life in patients with PD and burden reduction in their caregivers can be achieved through a systematic program of specialized enhanced rehabilitation interventions.

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