Is lamotrigine a teratogen?

Aim: To assess whether lamotrigine (Lamictal), when used in antiseizure medication (ASM) monotherapy, is a teratogen.

Materials/methods: Analysis of data from 490 LTG monotherapy treated pregnancies and 214 pregnancies in women with epilepsy not exposed to any antiseizure medications during at least the first half of pregnancy.

Results: The LTG-treated and the untreated pregnancies were well matched in nearly all regards apart from ASM exposure.

Corpus callosotomy for intractable epilepsy: a contemporary series of operative factors and the overall complication rate.

Objective: Corpus callosotomy is an effective treatment for atonic seizures in patients with medically refractory epilepsy. A large modern series of corpus callosotomies performed via open craniotomy highlights the importance of establishing contemporary complication rates for this operation as a benchmark for comparison with newer methodologies. The authors' study, therefore, examined operative factors and complication rates for a sample of patients who underwent open microsurgical craniotomy for corpus callosotomy to determine current metrics regarding safety and effectiveness for this procedure.

Reaching the potential of electron diffraction.

Microcrystal electron diffraction (MicroED) is an emerging structural technique in which submicron crystals are used to generate diffraction data for structural studies. Structures allow for the study of molecular-level architecture and drive hypotheses about modes of action, mechanisms, dynamics, and interactions with other molecules. Combining cryoelectron microscopy (cryo-EM) instrumentation with crystallographic techniques, MicroED has led to three-dimensional structural models of small molecules, peptides, and proteins and has generated tremendous interest due to its ability to use vanishingly small crystals.

Teratogenicity of zonisamide and other little-used antiseizure medications.

Purpose: To investigate the risk of teratogenesis occurring in relation to intrauterine exposure to infrequently used antiseizure medications in Australia.

Methods: Analysis of data contained in the Raoul Wallenberg Australian Pregnancy Register of Antiepileptic Drugs.

Results: There was statistically significant evidence that zonisamide, but not any other of nine infrequently used antiseizure medications in Australia, was associated with a risk of teratogenesis related to the maternal dose of the drug taken in at least the earlier half of pregnancy.

Staged Resection of Difficult-to-Treat Intracranial Meningiomas: A Systematic Review of the Indications, Surgical Approaches, and Postoperative Outcomes.

 Meningiomas-the most common extra-axial tumors-are benign, slow-growing dural-based lesions that can involve multiple cranial fossae and can progress insidiously for years until coming to clinical attention secondary to compression of adjacent neurovascular structures. For complex, multicompartmental lesions, multistaged surgeries have been increasingly shown to enhance maximal safe resection while minimizing adverse sequela. Here, we systematically review the extant literature to highlight the merits of staged resection.

Pregnancy, antiseizure medications and unexplained intrauterine foetal death.

Objective: To assess the role of antiseizure medication (ASM) regimens and other factors in relation to the occurrence of intrauterine foetal death (IUFD) in pregnant women with epilepsy (WWE) enrolled in the Raoul Wallenberg Australian Pregnancy Register of Antiepileptic Drugs (APR).

Results: IUFDs occurred in 70 (3.01 %) of 2,323 prospective pregnancies from WWE with known outcomes in the APR.

The effect of different antibiotic combinations in calcium sulfate cement on the growth of Cutibacterium acnes and Staphylococcus periprosthetic shoulder infection isolates.

Background: Periprosthetic joint infections (PJI) of the shoulder are a devastating complication of shoulder arthroplasty and are commonly caused by Staphylococcus and Cutibacterium acnes. Absorbable calcium sulfate (CS) beads are sometimes used for delivering antibiotics in PJI. This study evaluates the in vitro effect of different combinations of gentamicin, vancomycin, and ertapenem in beads made from CS cement on the growth of C acnes and coagulase-negative Staphylococcus (CNS) strains.

Asparagine-85 Stabilizes a Structural Active Site Water Network in CYP121A1 of .

The cytochrome P450 enzyme CYP121A1 endogenously catalyzes the formation of a carbon-carbon bond between the two phenol groups of dicyclotyrosine (cYY) in (Mtb). One of 20 CYP enzymes in Mtb, CYP121A1 continues to garner significant interest as a potential drug target. The accompanying reports the use of F NMR spectroscopy, reconstituted activity assays, and molecular dynamics simulations to investigate the significance of hydrogen bonding interactions that were theorized to stabilize a static active site water network.

The teratogenesis risk associated with antiseizure medication duotherapy in women with epilepsy.

Purpose: To investigate rates of occurrence of pregnancies associated with a foetal malformation (FM pregnancy rates) following simultaneous intrauterine exposure to two antiseizure medications in 524 pregnancies in women with epilepsy from the Australian Pregnancy Register who were treated simultaneously with various combinations and dosages of two antiseizure medications (duotherapy).

Results: FM pregnancy rates tended to be higher in those exposed simultaneously to two antiseizure medications, each of which was a statistically significant teratogen (valproate, topiramate, or carbamazepine), than when there was exposure to only one such teratogen. When there was exposure to only one such teratogen together with clonazepam or levetiracetam, for neither of which there was statistically significant evidence of heightened teratogenicity, the FM pregnancy rates also tended to be higher, but less so.

Changes over 24 years in a pregnancy register - Teratogenicity and epileptic seizure control.

Objectives: To trace (i) changes in Australian Pregnancy Register (APR) records concerning antiseizure medications (ASMs) prescribed for women with epilepsy (WWE) over the course of 24 years and correlate the changes with (ii) rates of occurrence of pregnancies involving foetal malformations, (iii) the body organs involved in the malformations, and (iv) freedom from epileptic seizures.

Results: Use of valproate and carbamazepine decreased progressively, use of lamotrigine remained relatively static, and the use of levetiracetam increased progressively, whereas the use of topiramate first increased and then fell again, associated with a temporary increase in malformation-associated pregnancy rate. More serious malformations, such as spina bifida, became less frequent, whereas more trivial ones tended to increase, whereas epileptic seizure freedom rates improved.

Pre-Diagnosis Dietary Patterns and Risk of Multiple Myeloma in the NIH-AARP Diet and Health Study.

Background: Despite patient interest in knowing whether diet is linked to multiple myeloma (MM), there is limited research on dietary patterns and MM risk. Two studies have assessed this risk, albeit with a small number of MM cases. The EPIC-Oxford cohort and Oxford Vegetarian study (65 MM cases) showed that fish eaters, vegetarians and vegans had significantly reduced MM risk compared to meat eaters.

Celebrating 100 years of Cope's Early Diagnosis of the AcuteAbdomen.

Background: No list of the iconic books in surgery would be complete without The Early Diagnosis of the Acute Abdomen by Sir Vincent Zachary Cope, MS, MD. First published in 1921, few books have stood the test of time like this treatise on the acute abdomen. It is also fitting that, after Mr Cope's passing, William Silen would assume the mantle with the 15th edition and maintain his legacy work through the 22nd and final edition.

Structural basis of bidirectional allostery across the heme in a cytochrome P450 enzyme.

Cytochromes P450 (CYPs) are heme-containing enzymes that are present in all kingdoms of life and share a structurally homologous, globular protein fold. CYPs utilize structures distal to the heme to recognize and coordinate substrates, while the necessary interactions with redox partner proteins are mediated at the opposite, proximal surface. In the current study, we investigated the functional allostery across the heme for the bacterial enzyme CYP121A1, which utilizes a non-polar distal-to-distal dimer interface for specific binding of its dicyclotyrosine substrate.

Application of multi-spectral CT imaging in Crohn's disease: a systematic review.

Background: No quantitative computed tomography (CT) biomarker is actually sufficiently accurate to assess Crohn's disease (CD) lesion activity, with adequate precision to guide clinical decisions.

Purpose: To assess the available literature on the use of iodine concentration (IC), from multi-spectral CT acquisition, as a quantitative parameter able to distinguish healthy from affected bowel and assess CD bowel activity and heterogeneity of activity along the involved segments.

Material And Methods: A literature search was conducted to identify original research studies published up to February 2022.

Specific fetal malformations following intrauterine exposure to antiseizure medication.

Objective: To investigate in the Australian Pregnancy Register of Antiepileptic Drugs patterns of fetal malformation associated with intrauterine exposure to particular currently available antiseizure medications taken by women with epilepsy.

Results: There was statistically significant evidence (P < 0.05) of an increased hazard of fetal malformation associated with exposure to valproate, carbamazepine, topiramate, zonisamide, and with conception after assisted fertilization, but a reduced hazard in the offspring of women who continued to smoke during pregnancy.

Exercise intolerance associated with impaired oxygen extraction in patients with long COVID.

Objective: Chronic mental and physical fatigue and post-exertional malaise are the more debilitating symptoms of long COVID-19. The study objective was to explore factors contributing to exercise intolerance in long COVID-19 to guide development of new therapies. Exercise capacity data of patients referred for a cardiopulmonary exercise test (CPET) and included in a COVID-19 Survivorship Registry at one urban health center were retrospectively analyzed.

Active Site Aromatic Residues Play a Dual Role in the Substrate Interaction and Protein Structure in Functional Dimers of CYP121A1 of .

The essential enzyme CYP121A1 of forms a functional dimer, which when disrupted results in a decrease of activity and substrate specificity. The crystal structure of CYP121A1 in complex with its substrate di-cyclotyrosine (cYY) indicates that the aromatic side chains of Phe-168 and Trp-182 form stabilizing π-π interactions with a tyrosyl ring of cYY. In the enclosed study, we utilize targeted F labeling of aromatic residues to label CYP121A1 for detection by nuclear magnetic resonance (NMR) spectroscopy.

Approximately One Half of Patients Greater Than 40 Years Old Achieve Patient Acceptable Symptomatic State 6 Months After Arthroscopic Partial Meniscectomy.

Purpose: The purposes of this study were to 1) calculate the minimal clinically important difference (MCID) in a population of patients undergoing arthroscopic partial meniscectomy (APM) based on Knee Injury and Osteoarthritis Outcomes Scores (KOOS), 2) quantify the difference between the proportion of patients reaching MCID based on KOOS versus the proportion who considered surgery to be successful based on a "yes" answer to a patient acceptable symptom state (PASS) question, and 3) calculate the percentage of patients experiencing treatment failure (TF).

Methods: A large, single-institution clinical database was queried for patients undergoing isolated APM (>40 years of age). Data were collected at regular time intervals, including KOOS and PASS outcome measures.

The regulation of a pigmentation gene in the formation of complex color patterns in Drosophila abdomens.

Changes in the control of developmental gene expression patterns have been implicated in the evolution of animal morphology. However, the genetic mechanisms underlying complex morphological traits remain largely unknown. Here we investigated the molecular mechanisms that induce the pigmentation gene yellow in a complex color pattern on the abdomen of Drosophila guttifera.