Crystal Polymorph Search in the NPT Ensemble via a Deposition/Sublimation Alchemical Path.

The formulation of active pharmaceutical ingredients involves discovering stable crystal packing arrangements or polymorphs, each of which has distinct pharmaceutically relevant properties. Traditional experimental screening techniques utilizing various conditions are commonly supplemented with in silico crystal structure prediction (CSP) to inform the crystallization process and mitigate risk. Predictions are often based on advanced classical force fields or quantum mechanical calculations that model the crystal potential energy landscape but do not fully incorporate temperature, pressure, or solution conditions during the search procedure. This study proposes an innovative alchemical path that utilizes an advanced polarizable atomic multipole force field to predict crystal structures based on direct sampling of the NPT ensemble. The use of alchemical (i.e., nonphysical) intermediates, a novel Monte Carlo barostat, and an orthogonal space tempering bias combine to enhance the sampling efficiency of the deposition/sublimation phase transition. The proposed algorithm was applied to 2-((4-(2-(3,4-dichlorophenyl)ethyl)phenyl)amino)benzoic acid (Cambridge Crystallography Database Centre ID: XAFPAY) as a case study to showcase the algorithm. Each experimentally determined polymorph with one molecule in the asymmetric unit was successfully reproduced via approximately 1000 short 1 ns simulations per space group where each simulation was initiated from random rigid body coordinates and unit cell parameters. Utilizing two threads of a recent Intel CPU (a Xeon Gold 6330 CPU at 2.00 GHz), 1 ns of sampling using the polarizable AMOEBA force field can be acquired in 4 h (equating to more than 300 ns/day using all 112 threads/56 cores of a dual CPU node) within the Force Field X software (https://ffx.biochem.uiowa.edu). These results demonstrate a step forward in the rigorous use of the NPT ensemble during the CSP search process and open the door to future algorithms that incorporate solution conditions using continuum solvation methods.

Elective Cesarean Section during Preterm Prevents Pulmonary Hypoplasia Development in Potter Sequence.

Potter syndrome, first reported in 1946 by Edith Potter, refers to fatal cases of bilateral renal aplasia with pulmonary hypoplasia, peculiar facial features, and limb deformities. Presently, patients with oligohydramnios showing similar pathological manifestations due to oligohydramnios caused by conditions other than bilateral renal aplasia have been reported, and are known as the Potter sequence. There are limited studies and unclear guidelines on the safest delivery time and detailed postpartum management for patients with the Potter sequence. We experienced a case of Potter sequence, in which the patient was born by elective cesarean section at gestational age (GA) of 34 weeks. Fetal ultrasound at GA of 26 weeks 4 days showed oligohydramnios, multilocular cystic lesions in the left kidney, and an absent right kidney. Prenatal fetal MRI at GA of 33 weeks and 3 days showed pulmonary hypoplasia, and the ratio of fetal lung volume (FLV) to fetal body weight (FBW) was 0.0135 ml/g. We suspected that the fetal lung could not grow because of persistent oligohydramnios, which leads to a further decline in the ratio of FLV to FBW during pregnancy. We performed a cesarean section at GA of 34 weeks to prevent the exacerbation of the imbalance between lung volume and physique. We struggled to keep her condition stabilized with strict management of her respiratory condition, dialysis, and nutrition. She was discharged from the hospital at 169 days of age. Elective caesarean section in the term of premature birth prevented the progression of pulmonary hypoplasia and made it possible to save her life. Potter sequence is still relatively unknown, and it is necessary for more studies to be conducted in the future.

Chemical synthesis and antifouling activity of monoterpene-furan hybrid molecules.

Geraniol, a monoterpene, and furan are structural motifs that exhibit antifouling activity. In this study, monoterpene-furan hybrid molecules with potentially enhanced antifouling activity were designed and synthesized. The nine synthetic hybrids showed antifouling activity against the cypris larvae of the barnacle Balanus (Amphibalanus) amphitrite with EC50 values of 1.65-4.70 µg mL-1. This activity is higher than that of geraniol and the reference furan compound. This hybridization approach to increase antifouling activity is useful and can also be extended to other active structural units.

Oral to nasal endotracheal tube exchange using tracheal tube guide and video laryngoscope in a pediatric patient with facial burns: a case report.

BACKGROUND: Airway management in children with severe burns is difficult because of airway edema and prolonged duration of ventilatory management. There is insufficient evidence to suggest that tracheostomy is beneficial for children. CASE PRESENTATION: A male child aged 1 year and 4 months was injured when he accidentally fell into a bathtub filled with boiling water. Furthermore, 85% of the burnt area, including the face and neck, consisted of second-degree burns; hence, oral tracheal intubation and resuscitative infusion were required. In this case, the patient was safely switched from oral to nasotracheal intubation using a tracheal tube guide and video laryngoscope, without the use of a bronchoscope, and ventilatory management could be continued for 2 weeks. CONCLUSION: Oral to nasal endotracheal tube exchange using a tracheal tube guide and video laryngoscope may be useful not only for pediatric burn patients but also for adult patients who need to be safely switched from oral to nasotracheal intubation.

Infection-Induced Elevated Plasma Perampanel in a Patient with Hemimegalencephaly.

Perampanel is a noncompetitive, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid glutamate receptor antagonist. Herein, we report a case of increased perampanel plasma concentration and impaired consciousness triggered by an infection. The patient had refractory epilepsy associated with hemimegalencephaly. During adolescence, perampanel (maximum dose, 10 mg, oral), valproic acid, clobazam, and lacosamide were administered for seizure control. He was admitted to our hospital with high fever, impaired consciousness, and elevated perampanel plasma level (from 1,300 to 1,790 ng/mL), but with no increase in the concentration of other antiseizure medications. Further examinations (blood, cerebrospinal fluid, brain magnetic resonance images, and electroencephalogram) revealed no physical cause for impaired consciousness. After discontinuation of perampanel, his level of consciousness gradually improved. The pharmacokinetics of perampanel may be modified by both hemimegalencephaly and infection, resulting in an elevated plasma concentration of perampanel. This case underlines the importance of monitoring perampanel plasma concentration in patients with underlying brain disease who develop an infection.

Recent Progress in Development of Carbon-Nanotube-Based Photo-Thermoelectric Sensors and Their Applications in Ubiquitous Non-Destructive Inspections.

The photo-thermoelectric (PTE) effect in electronic materials effectively combines photo-absorption-induced local heating and associated thermoelectric conversion for uncooled and broadband photo-detection. In particular, this work comprehensively summarizes the operating mechanism of carbon nanotube (CNT)-film-based PTE sensors and ubiquitous non-destructive inspections realized by exploiting the material properties of CNT films. Formation of heterogeneous material junctions across the CNT-film-based PTE sensors, namely photo-detection interfaces, triggers the Seebeck effect with photo-absorption-induced local heating. Typical photo-detection interfaces include a channel-electrode boundary and a junction between P-type CNTs and N-type CNTs (PN junctions). While the original CNT film channel exhibits positive Seebeck coefficient values, the material selections of the counterpart freely govern the intensity and polarity of the PTE response signals. Based on these operating mechanisms, CNT film PTE sensors demonstrate a variety of physical and chemical non-destructive inspections. The device aggregates broad multi-spectral optical information regarding the targets and reconstructs their inner composite or layered structures. Arbitrary deformations of the device are attributed to the macroscopic flexibility of the CNT films to further monitor targets from omni-directional viewing angles without blind spots. Detection of blackbody radiation from targets using the device also visualizes their behaviors and associated changes.

Transcription factor YY1 interacts with retroviral integrases and facilitates integration of moloney murine leukemia virus cDNA into the host chromosomes.

Retroviral integrases associate during the early viral life cycle with preintegration complexes that catalyze the integration of reverse-transcribed viral cDNA into the host chromosomes. Several cellular and viral proteins have been reported to be incorporated in the preintegration complex. This study demonstrates that transcription factor Yin Yang 1 binds to Moloney murine leukemia virus, human immunodeficiency virus type 1, and avian sarcoma virus integrases. The results of coimmunoprecipitation and in vitro pulldown assays revealed that Yin Yang 1 interacted with the catalytic core and C-terminal domains of Moloney murine leukemia virus and human immunodeficiency virus type 1 integrases, while the transcriptional repression and DNA-binding domains of the Yin Yang 1 molecule interacted with Moloney murine leukemia virus integrase. Immunoprecipitation of the cytoplasmic fraction of virus-infected cells followed by Southern blotting and chromatin immunoprecipitation demonstrated that Yin Yang 1 associated with Moloney murine leukemia virus cDNA in virus-infected cells. Yin Yang 1 enhanced the in vitro integrase activity of Moloney murine leukemia virus, human immunodeficiency virus type 1, and avian sarcoma virus integrases. Furthermore, knockdown of Yin Yang 1 in host cells by small interfering RNA reduced Moloney murine leukemia virus cDNA integration in vivo, although viral cDNA synthesis was increased, suggesting that Yin Yang 1 facilitates integration events in vivo. Taking these results together, Yin Yang 1 appears to be involved in integration events during the early viral life cycle, possibly as an enhancer of integration.