Reproductive Safety of Trazodone After Maternal Exposure in Early Pregnancy: A Comparative ENTIS Cohort Study.

PURPOSE/BACKGROUND: Trazodone is indicated for the treatment of major depressive disorder, but more frequently prescribed off-label at lower doses for insomnia in women of childbearing age. The aim of this study was to assess the risks linked to trazodone exposure during pregnancy for which limited safety data are available. METHODS/PROCEDURES: This multicenter, observational prospective cohort study compared pregnancy outcomes in women exposed to trazodone in early pregnancy against those in a reference group of women exposed to a selective serotonin reuptake inhibitors (SSRIs) between 1996 and 2021. FINDINGS/RESULTS: The sample included 221 trazodone and 869 SSRI-exposed pregnancies. Exposure to trazodone in the first trimester was not associated with a significant difference in the risk of major congenital anomalies (trazodone [1/169, 0.6%]; SSRI [19/730, 2.6%]; adjusted odds ratio, 0.2; 95% confidence interval, 0.03-1.77). The cumulative incidences of live birth were 61% and 73% in the trazodone and reference group, respectively (25% vs 18% for pregnancy loss and 14% vs 10% for pregnancy termination). Trazodone exposure was not associated with a significantly increased risk of pregnancy termination and pregnancy loss. The rate of small for gestational age infants did not differ between the groups. IMPLICATIONS/CONCLUSIONS: This study did not reveal a significant difference in the risk of major congenital anomalies after first trimester exposure to trazodone, compared with SSRI exposure. Although this study is the largest so far, these results call for confirmation through further studies.

A critical appraisal of controlled studies investigating malformation risks following pregabalin use in early pregnancy.

In March 2022, the Summary of Product Characteristics for the Lyrica brand of pregabalin was updated with warnings regarding malformation risks. This literature review and critical appraisal aims to explore whether these Summary of Product Characteristics updates are justified and provide clarity on the risk-benefit balance for pregabalin use in early pregnancy. A literature review was conducted in May 2022 to identify English language comparative studies of any design providing data about first trimester maternal pregabalin use and malformation risk. Five observational comparative cohort studies using data from 9 distinct datasets were located. Collectively these studies described at least 5300 unique pregabalin exposed pregnancies, with 4900 exposed in at least the first trimester. Three studies investigated overall major malformation risks, and 4 investigated specific malformation risks. The available evidence was found to be conflicting and generally of low quality, probably influenced by bias and data confounding, with no clear pattern of specific malformations observed. Findings from the largest study suggested absolute risks of major malformation of 4.8-5.6%, relative to a background risk of approximately 4%. Due to study methodology limitations, the available data were judged to only provide low quality evidence suggestive of a possible and unconfirmed small increased risk that cannot be solely attributed to foetal pregabalin exposure. This literature review and critical appraisal indicates that the Lyrica product literature updates are insufficiently substantiated and could result in confusion and misinformed clinical risk-benefit decision making.

Combining forces for causal reasoning: Children's predictions about physical interactions.

Reasoning about causal relations is essential for children's early cognitive development. The current study investigated 4-year-olds' (N = 58) reasoning about complex causal physical interactions in terms of predicting the endpoint of motion. In an online task, children were presented with four configurations that involved different interactions of forces and consequently different patterns of motion. These were Cause (one force moving an object), Enable (a secondary force promoting the motion), Prevent-180° (an opposing force hindering the motion), and Prevent-90° (two-dimensional; a perpendicular force altering the motion). Each prediction was made in terms of either the Distance or Direction of the motion, which was novel in this task compared with previous assessments. Results revealed differences between the configurations, with Cause being the easiest and Prevent-90° being the most difficult to predict. Furthermore, predictions were more accurate when options were about the motion's Direction, whereas Distance options may have aggravated reasoning. The current study extends previous findings on children's intuitive physics and causal cognition by showing that accuracy in reasoning not only is dependent on the number of forces and dimensions at work but also interacts with estimating the motion's Distance and Direction.

Any way the wind blows: Children's inferences about force and motion events.

Göksun, George, Hirsh-Pasek, and Golinkoff (2013) used force dynamics, or the semantic categories defined by spatial arrays of forces, to study the development of preschoolers' predictions about the outcomes of forces working in concert. The current study extends this approach to problems requiring inferences about causal factors. In total, 30 5- and 6-year-old children were asked to identify and coordinate forces to achieve a result. Problems varied in the number and orientation of forces, mirroring spatial arrays characteristic of categories like prevent (i.e., opposing forces). Children successfully inferred causes of single- and dual-force events, performing best when problems reflected the spatial arrays of forces described in language. Results support force dynamics as a valuable framework for the development of force and motion representations.

Manganese Tetraboride, MnB4: High-Temperature Crystal Structure, p-n Transition, (55)Mn NMR Spectroscopy, Solid Solutions, and Mechanical Properties.

The structural and electronic properties of MnB4 were studied by high-temperature powder X-ray diffraction and measurements of the conductivity and Seebeck coefficient on spark-plasma-sintered samples. A transition from the room-temperature monoclinic structure (space group P2(1)/c) to a high-temperature orthorhombic structure (space group Pnnm) was observed at about 650 K. The material remained semiconducting after the transition, but its behavior changed from p-type to n-type. (55)Mn NMR measurements revealed an isotropic chemical shift of -1315 ppm, confirming an oxidation state of Mn close to I. Solid solutions of Cr(1-x)Mn(x)B4 (two phases in space groups Pnnm and P2(1)/c) were synthesized for the first time. In addition, nanoindentation studies yielded values of (496±26) and (25.3±1.7) GPa for the Young's modulus and hardness, respectively, compared to values of 530 and 37 GPa obtained by DFT calculations.

Increasing frequency of severe clinical toxicity after use of 2,4-dinitrophenol in the UK: a report from the National Poisons Information Service.

OBJECTIVE: 2,4-Dinitrophenol (DNP) increases energy consumption by uncoupling oxidative phosphorylation. Although not licensed as a medicine, it is sometimes used by 'body sculptors' and for weight loss as a 'fat burning' agent. This research was performed to characterise patterns of presentation, clinical features and outcomes of patients reported to the National Poisons Information Service (NPIS) in the UK after exposure to DNP. METHODS: NPIS telephone enquiry records and user sessions for TOXBASE, the NPIS online information database, related to DNP, were reviewed from 1 January 2007 to 31 December 2013. RESULTS: Of the 30 separate systemic exposures to DNP reported by telephone to NPIS during the study period (27 males, 3 females, with a median age of 23.5 years), there were 3 during 2007-2011 (inclusive), 5 during 2012 and 22 during 2013. TOXBASE user sessions also increased sharply from 6 in 2011 to 35 in 2012 and 331 in 2013. The modes of exposure reported in telephone enquiries were chronic (n=2), acute (n=12) and subacute (n=16). Commonly reported clinical features were fever (47%), tachycardia (43%), sweating (37%), nausea or vomiting (27%), skin discolouration or rash (23%), breathing difficulties (23%), abdominal pain (23%), agitation (13%) and headache (13%). There were five (17%, 95% CI 6.9% to 34%) fatalities, four involving acute overdose. CONCLUSIONS: The study indicates a substantial recent increase in clinical presentations with toxicity caused by exposure to DNP in the UK with an associated high mortality. Further steps are needed to warn potential users of the severe and sometimes fatal toxicity that may occur after exposure to this compound.

Mesostructure from hydration gradients in demosponge biosilica.

Organisms of the phylum Porifera, that is, sponges, utilize enzymatic hydrolysis to concatenate bioavailable inorganic silicon to produce lightweight, strong, and often flexible skeletal elements called spicules. In their optical transparency, these remarkable biomaterials resemble fused silica, despite having been formed under ambient marine biological conditions. Although previous studies have elucidated the chemical mechanisms of spicule formation and revealed the extensive hydration of these glasses, their precise composition and local and medium-range structures had not been determined. We have employed a combination of compositional analysis, (1) H and (29) Si solid-state nuclear magnetic resonance spectroscopy, and synchrotron X-ray total scattering to characterize spicule-derived silica produced by the demosponge Tethya aurantia. These studies indicate that the materials are highly hydrated, but in an inhomogeneous manner. The spicule-derived silica is, on average, perfectly dense for the given extent of hydration and regions of fully condensed and unstrained SiO networks persist throughout each monolithic spicule. To accommodate chemical strain and defects, the extensive hydration is concentrated in distinct regions that give rise to mesostructural features. The chemistry responsible for producing spicule silica resembles hydrolytic sol-gel processing, which offers exceptional control over the precise local atomic arrangement of materials. However, the specific processing involved in forming the sponge spicule silica further results in regions of fully condensed silica coexisting with regions of incomplete condensation. This mesostructure suggests a mechanism for atomistic defect tolerance and strain relief that may account for the unusual mechanical properties of the biogenic spicules.

Peierls-distorted monoclinic MnB(4) with a Mn-Mn bond.

Tetraborides of chromium and manganese exhibit an unusual boron-atom framework that resembles the hypothetical tetragonal diamond. They are believed to be very hard. Single crystals of MnB4 have now been grown. The compound crystallizes in the monoclinic crystal system (space group P21 /c) with a structure that has four crystallographically independent boron-atom positions, as confirmed by (11) B MAS-NMR spectroscopy. An unexpected short distance between the Mn atoms suggests a double Mn-Mn bond and is caused by Peierls distortion. The structure was solved using group-subgroup-relationships. DFT calculations indicate Mn(I) centers and paramagnetism, as confirmed by magnetic measurements. The density of states shows a pseudo-band gap at the Fermi energy and semiconducting behavior was observed for MnB4 .

Clozapine-Related Functional Bowel Obstruction: A Rare Adverse Effect Unmasking Quetiapine and Benztropine Interaction Raising Need for Bowel Surveillance.

Randomized controlled trials demonstrate a significant decline in hospital admissions and length of stay following the initiation of clozapine in individuals with bipolar disorder and schizophrenia, along with an increase in quality-adjusted life years. The morbidity and mortality associated with clozapine-induced gastrointestinal hypomotility (CIGH) is greater than agranulocytosis. Despite this, we only have clozapine risk evaluation and mitigation strategies by the US Food and Drug Administration for white cell count monitoring, but none exists for CIGH. Our case highlights CIGH due to multiple factors and recommendations to prevent it and enhance clozapine compliance by conducting a thorough literature review.

Average and local structural origins of the optical properties of the nitride phosphor La(3-x)Ce(x)Si6N11 (0 < x ≤ 3).

Structural intricacies of the orange-red nitride phosphor system La(3-x)Ce(x)Si6N11 (0 < x ≤ 3) have been elucidated using a combination of state-of-the art tools, in order to understand the origins of the exceptional optical properties of this important solid-state lighting material. In addition, the optical properties of the end-member (x = 3) compound, Ce3Si6N11, are described for the first time. A combination of synchrotron powder X-ray diffraction and neutron scattering is employed to establish site preferences and the rigid nature of the structure, which is characterized by a high Debye temperature. The high Debye temperature is also corroborated from ab initio electronic structure calculations. Solid-state (29)Si nuclear magnetic resonance, including paramagnetic shifts of (29)Si spectra, are employed in conjunction with low-temperature electron spin resonance studies to probes of the local environments of Ce ions. Detailed wavelength-, time-, and temperature-dependent luminescence properties of the solid solution are presented. Temperature-dependent quantum yield measurements demonstrate the remarkable thermal robustness of luminescence of La2.82Ce0.18Si6N11, which shows little sign of thermal quenching, even at temperatures as high as 500 K. This robustness is attributed to the highly rigid lattice. Luminescence decay measurements indicate very short decay times (close to 40 ns). The fast decay is suggested to prevent strong self-quenching of luminescence, allowing even the end-member compound Ce3Si6N11 to display bright luminescence.

Forces and motion: how young children understand causal events.

How do children evaluate complex causal events? This study investigates preschoolers' representation of force dynamics in causal scenes, asking whether (a) children understand how single and dual forces impact an object's movement and (b) this understanding varies across cause types (Cause, Enable, Prevent). Three-and-a half- to 5.5-year-olds (n = 60) played a board game in which they were asked to predict the endpoint of a ball being acted upon by one or two forces. Children mostly understood the interactions of forces underlying each type of cause; only 5.5-year-olds could integrate two contradictory forces. Children perceive force interactions underlying causal events, but some concepts might not be fully understood until later in childhood. This study provides a new way of thinking about causal relations.

Chronic total occlusion rotational atherectomy (CTO RA) versus non-CTO RA in coronary artery disease: A meta-analysis of clinical outcomes and complications.

Background: Chronic total occlusion rotational atherectomy (CTO RA) is an emerging intervention in coronary artery disease (CAD), although data comparing its outcomes and complications with non-CTO RA are scarce. We sought to evaluate the outcomes of RA in CTO lesions compared to those in non-CTO lesions by performing a meta-analysis. Methods: We conducted a systematic review and meta-analysis of studies comparing the clinical outcomes and complications between CTO RA and non-CTO RA in patients with CAD. We searched PUBMED, CINAHL, EMBASE and Cochrane Central Register of Clinical Trials for any studies that compared the outcomes of RA in CTO and non-CTO lesions. The outcomes analyzed included in-hospital major adverse cardiovascular events (MACE), target vessel revascularization (TVR), angiographic success, procedural success, periprocedural complications, coronary perforation, and all-cause mortality. Results: Four studies with a total of 1868 patients were included, spanning from 2018 to 2022, from Germany, Taiwan, and Korea. The median age of included patients was 71. The rate of the pooled results indicated a moderate, non-significant increase in in-hospital MACE and TVR for CTO RA compared to non-CTO RA. There was a small, non-significant decrease in angiographic and procedural success in CTO RA compared to non-CTO RA. CTO RA was associated with a non-significant increase in periprocedural complications and a significant increase in coronary perforation compared to non-CTO RA. All-cause mortality showed a non-significant increase in the CTO RA group. Conclusion: This meta-analysis provides evidence that while CTO RA may be associated with a higher risk of coronary perforation, the risk of other outcomes including MACE, TVR, and all-cause mortality is not significantly different compared to non-CTO RA. More research is needed to further understand these relationships and to optimize treatment strategies in patients with CAD undergoing CTO RA.

Structure-directing roles and interactions of fluoride and organocations with siliceous zeolite frameworks.

Interactions of fluoride anions and organocations with crystalline silicate frameworks are shown to depend subtly on the architectures of the organic species, which significantly influence the crystalline structures that result. One- and two-dimensional (2D) (1)H, (19)F, and (29)Si nuclear magnetic resonance (NMR) spectroscopy measurements establish distinct intermolecular interactions among F(-) anions, imidazolium structure-directing agents (SDA(+)), and crystalline silicate frameworks for as-synthesized siliceous zeolites ITW and MTT. Different types and positions of hydrophobic alkyl ligands on the imidazolium SDA(+) species under otherwise identical zeolite synthesis compositions and conditions lead to significantly different interactions between the F(-) and SDA(+) ions and the respective silicate frameworks. For as-synthesized zeolite ITW, F(-) anions are established to reside in the double-four-ring (D4R) cages and interact strongly and selectively with D4R silicate framework sites, as manifested by their strong (19)F-(29)Si dipolar couplings. By comparison, for as-synthesized zeolite MTT, F(-) anions reside within the 10-ring channels and interact relatively weakly with the silicate framework as ion pairs with the SDA(+) ions. Such differences manifest the importance of interactions between the imidazolium and F(-) ions, which account for their structure-directing influences on the topologies of the resulting silicate frameworks. Furthermore, 2D (29)Si{(29)Si} double-quantum NMR measurements establish (29)Si-O-(29)Si site connectivities within the as-synthesized zeolites ITW and MTT that, in conjunction with synchrotron X-ray diffraction analyses, establish insights on complicated order and disorder within their framework structures.

Aortic Dissection Presenting as Leg Pain.

A female in her mid-sixties presented to the emergency department with the chief complaint of leg pain. After evaluation, she was found to have a rapidly progressing aortic dissection resulting in an occlusion of the right common iliac artery. The authors highlight the variable presentations of acute aortic dissection, beyond classic tearing chest pain.

Bounced off a Truck Out of the Blue: A Case Report of a Lightning Strike During a Thunderstorm.

Lightning strikes are a relatively uncommon emergency department presentation, and due to the very high energy involved, can present quite dramatically, including cardiac arrest. However, as with many chief complaints, sometimes these patients can be discharged home after a benign emergency department evaluation. We present one such case of a male who was struck to the ground by lightning outside his truck, which subsequently caught on fire. He demonstrated the classic Lichtenberg figures associated with a lightning injury that evolved over time but was otherwise hemodynamically stable. After an unremarkable laboratory evaluation and electrocardiogram, he was safely discharged home.

Stacking the evidence: Parents' use of acoustic packaging with preschoolers.

Segmenting continuous events into discrete actions is critical for understanding the world. As infants may lack top-down knowledge of event structure, caregivers provide audiovisual cues to guide the process, aligning action descriptions with event boundaries to increase their salience. This acoustic packaging may be specific to infant-directed speech, but little is known about when and why the use of this cue wanes. We explore whether acoustic packaging persists in parents' teaching of 2.5-5.5-year-old children about various toys. Parents produced a smaller percentage of action speech relative to studies with infants. However, action speech largely remained more aligned to action boundaries relative to non-action speech. Further, for the more challenging novel toys, parents modulated their use of acoustic packaging, providing it more for those children with lower vocabularies. Our findings suggest that acoustic packaging persists beyond interactions with infants, underscoring the utility of multimodal cues for learning, particularly for less knowledgeable learners in challenging learning environments.

Carving the world for language: how neuroscientific research can enrich the study of first and second language learning.

Linguistics, psychology, and neuroscience all have rich histories in language research. Crosstalk among these disciplines, as realized in studies of phonology, is pivotal for understanding a fundamental challenge for first and second language learners (SLLs): learning verbs. Linguistic and behavioral research with monolinguals suggests that infants attend to foundational event components (e.g., path, manner). Language then heightens or dampens attention to these components as children map word to world in language-specific ways. Cross-linguistic differences in semantic organization also reveal sources of struggles for SLLs. We discuss how better integrating neuroscience into this literature can unlock additional mysteries of verb learning.

A protected annealing strategy to enhanced light emission and photostability of YAG:Ce nanoparticle-based films.

A significant obstacle in the development of YAG:Ce nanoparticles as light converters in white LEDs and as biological labels is associated with the difficulty of finding preparative conditions that allow simultaneous control of structure, particle size and size distribution, while maintaining the optical properties of bulk samples. Preparation conditions frequently involve high-temperature treatments of precursors (up to 1400 °C), which result in increased particle size and aggregation, and lead to oxidation of Ce(iii) to Ce(iv). We report here a process that we term protected annealing, that allows the thermal treatment of preformed precursor particles at temperatures up to 1000 °C while preserving their small size and state of dispersion. In a first step, pristine nanoparticles are prepared by a glycothermal reaction, leading to a mixture of YAG and boehmite crystalline phases. The preformed nanoparticles are then dispersed in a porous silica. Annealing of the composite material at 1000 °C is followed by dissolution of the amorphous silica by hydrofluoric acid to recover the annealed particles as a colloidal dispersion. This simple process allows completion of YAG crystallization while preserving their small size. The redox state of Ce ions can be controlled through the annealing atmosphere. The obtained particles of YAG:Ce (60 ± 10 nm in size) can be dispersed as nearly transparent aqueous suspensions, with a luminescence quantum yield of 60%. Transparent YAG:Ce nanoparticle-based films of micron thickness can be deposited on glass substrates using aerosol spraying. Films formed from particles prepared by the protected annealing strategy display significantly improved photostability over particles that have not been subject to such annealing.

Efficacy of cone-beam computed tomography as a modality to accurately identify the presence of second mesiobuccal canals in maxillary first and second molars: a pilot study.

INTRODUCTION: The achievement of successful nonsurgical endodontic therapy relies on the location, disinfection, and obturation of all canals in the root canal system. This study evaluated the ability of the i-CAT cone-beam computed tomography (CBCT) unit (Imaging Sciences International, Hatfield, PA) to accurately identify the presence or absence of the second mesiobuccal canal (MB2) in maxillary first and maxillary second human molars. METHODS: Twenty completely intact maxillary first and second molars were used as test subjects. The existence of the MB2 canal was evaluated by the following three methods: (1) periapical radiograph evaluation, (2) CBCT evaluation, and (3) clinical sectioning evaluation. The evaluation methods were used to compare the accuracy of CBCT scanning and clinical sectioning (gold standard) in the identification of the MB2 canal. RESULTS: The i-CAT CBCT unit accurately identified the presence or absence of the MB2 canal in 78.95% of samples. Statistical analysis showed that there was no significant difference in the ability of CBCT scanning to detect the MB2 canal when compared with the gold standard of clinical sectioning (p > 0.5). CONCLUSION: The results of this in vitro investigation may be interpreted to show that CBCT scanning is a reliable method to detect the MB2 canal when compared with the gold standard of physical sectioning of the specimen.