The neurorehabilitation of post-stroke dysphagia: Physiology and pathophysiology.

Swallowing is a complex process involving the precise contractions of numerous muscles of the head and neck, which act to process and shepherd ingested material from the oral cavity to its eventual destination, the stomach. Over the past five decades, information from animal and human studies has laid bare the complex network of neurones in the brainstem, cortex and cerebellum that are responsible for orchestrating each normal swallow. Amidst this complexity, problems can and often do occur that result in dysphagia, defined as impaired or disordered swallowing. Dysphagia is common, arising from multiple varied disease processes that can affect any of the neuromuscular structures involved in swallowing. Post-stroke dysphagia (PSD) remains the most prevalent and most commonly studied form of dysphagia and, as such, provides an important disease model to assess dysphagia physiology and pathophysiology. In this review, we explore the complex neuroanatomical processes that occur during normal swallowing and PSD. This includes how strokes cause dysphagia, the mechanisms through which natural neuroplastic recovery occurs, current treatments for patients with persistent dysphagia and emerging neuromodulatory treatments.

"On-the-fly" Crystal : How to reliably and automatically characterize and construct potential energy surfaces.

In this work, the Crystal  code, developed previously by the authors to find "holes" as well as legitimate transition states in existing potential energy surface (PES) functions [JPC Lett. 11, 6468 (2020)], is retooled to perform on-the-fly "direct dynamics"-type PES explorations, as well as automatic construction of new PES functions. In all of these contexts, the chief advantage of Crystal  over other methods is its ability to globally map the PES, thereby determining the most relevant regions of configuration space quickly and reliably-even when the dimensionality is rather large. Here, Crystal  is used to generate a uniformly spaced grid of density functional theory (DFT) or ab initio points, truncated over the relevant regions, which can then be used to either: (a) hone in precisely on PES features such as minima and transition states, or; (b) create a new PES function automatically, via interpolation. Proof of concept is demonstrated via application to three molecular systems: water (H 2 O), (reduced-dimensional) methane (CH 4 ), and methylene imine (CH 2 NH).

Developing a Passive Dosing Method for Acute Aquatic Toxicity Tests of Cationic Surfactant Benzalkoniums (BACs).

Benzalkonium chlorides (BACs) have been of environmental concern due to their widespread use and potential harm. However, challenges arise in defining and controlling the exposure concentration (Cw) in aquatic toxicity tests involving BACs with a long alkyl chain (i.e., #C > 14). To address this, a novel passive dosing method was introduced in the 48 h-acute ecotoxicity test on Daphnia magna and compared to the conventional solvent-spiking method in terms of Cw stability and toxicity results. Among 13 sorbent materials tested for their sorption capacity, poly(ether sulfone) (PES) membrane was an optimal passive dosing reservoir, with equilibrium desorption of BACs to water achieved within 24 h. The Cw of BACs remained constant in both applied dosing methods during the test period. However, the Cw in solvent-spiking tests was lower than the nominal concentration for long-chain BACs, particularly at low exposure concentrations. Notably, the solvent-spiking tests indicated that the toxicity of BACs increased with alkyl chain length from C6 to 14, followed by a decline in toxicity from C14 to 18. In contrast, the passive dosing method displayed similar or slightly increasing toxicity levels of BACs from C14 to C18, indicating higher toxicity of C16 and C18-BACs than that inferred by the solvent spiking test. These findings emphasize the potential of applying this innovative passive dosing approach in aquatic toxicity tests to generate reliable and accurate toxicity data and support a comprehensive risk assessment of cationic surfactants.

Anatomical studies on the PES region of Zebu cattle (Bos Taurus indicus) with special references to 3D computed tomography imaging technique.

The 3D render volume reconstruction CT (3D-RVCT) produced detailed images of the PES region, determining its relationships with the surrounding structures. Despite extensive research in veterinary studies on the PES through gross anatomy and CT, there is a lack of studies on the PES of zebu cattle. The study aimed to analyze the PES of Zebu cattle using gross cross-sectional, radiographic, CT, and morphometric methods, with the use of 3D-RVCT to provide anatomical guidance for surgeons and students. The study was performed on sixteen PES regions to provide hard and soft tissues in CT images. Three are five tarsal bones and two large fused (III and IV) metatarsal bones that were completely fused except for their distal extremities, which were divided distally by the intertrochlear notch. The cortical thickness of the metatarsal bone was equal on both sides. The bony septum divided the medullary cavity between the two fused large metatarsal bones in the proximal distal half only and disappeared in the middle part. The reconstruction showed similar sizes in the right and left limbs, confirming the pes bones. The radiographic and CT images could be used as a normal reference for the interpretation of some clinical diseases in the PES. The 3D CT reconstruction of the pes bones was described by various CT oblique dorsal and plantar views. The study focuses on diagnosing PES disorders using CT imaging, improving medical interventions, improving Zebu cattle health outcomes, and empowering students to contribute to veterinary medicine research and advancements.

Duration and outcome of orthotic treatment in children with clubfoot - a four-year follow-up national register study of Swedish children born between 2015 and 2017.

BACKGROUND: The Ponseti method for treating clubfoot consists of initial treatment with serial casting accompanied by achillotenotomy if needed, followed by the maintenance phase including treatment with a foot abduction orthosis (FAO) for at least four years. This study aimed to examine the duration, course, and outcome of orthotic treatment in children with clubfoot. METHODS: 321 children with clubfoot, born between 2015 and 2017, registered in the Swedish Pediatric Orthopedic Quality Register (SPOQ), were included in this prospective cohort study. Data on deformity characteristics and orthotic treatment were extracted. For children with bilateral clubfoot, one foot was included in the analysis. RESULTS: Of the 288 children with isolated clubfoot, 274 children (95.5%) were prescribed an FAO, and 100 children (35%) changed orthosis type before 4 years of age. Of the 33 children with non-isolated clubfoot, 25 children (76%) were prescribed an FAO, and 21 children (64%) changed orthosis type before 4 years of age. 220 children with isolated clubfoot (76%), and 28 children with non-isolated clubfoot (84%) continued orthotic treatment until 4 years of age or longer. Among children with isolated clubfoot, children ending orthotic treatment before 4 years of age (n = 63) had lower Pirani scores at birth compared to children ending orthotic treatment at/after 4 years of age (n = 219) (p = 0.01). It was more common to change orthosis type among children ending orthotic treatment before 4 years of age (p = 0.031). CONCLUSIONS: The majority of children with clubfoot in Sweden are treated with an FAO during the maintenance phase. The proportion of children changing orthosis type was significantly greater and the Pirani score at diagnosis was lower significantly among children ending orthotic treatment before 4 years of age. Long-term follow-up studies are warranted to fully understand how to optimize, and individualize, orthotic treatment with respect to foot involvement and severity of deformity. LEVEL OF EVIDENCE: II.

Pharyngeal Cavity Electrical Stimulation-Assisted Swallowing for Post-stroke Dysphagia: A Systematic Review and Meta-analysis of Randomized Controlled Studies.

Stroke is the leading cause of death and disability among adults. The incidence of stroke per 100, 000 patient-years was 2875. As many as 37% to 78% of patients with acute strokes suffer dysphagia. Dysphagia can easily lead to inhalation pneumonia, dehydration, malnutrition, and other serious complications, affecting the quality of life of stroke patients and increasing their mortality. Effective prevention and treatment of post-stroke dysphagia are of great significance to improving the prognosis and quality of life of patients. Some studies have shown that Pharyngeal cavity electrical stimulation-assisted swallowing (PCES-assisted swallowing) has a positive effect on patients with post-stroke dysphagia. This study will evaluate the effects of PCES-assisted swallowing on post-stroke dysphagia, including swallowing function, withdrawal rate of nasal feeding tubes, duration of hospitalization, and so on. Randomized controlled trials (RCTs) of PCES-assisted swallowing in the treatment of post-stroke dysphagia were searched in eight databases, including Cochrane Library, Embase, PubMed, Web of Science, Chinese Biomedical Literature Database, VIP Information Resource System, CNKI, and Wanfang Medical Science. The retrieval time was from the database establishment to June 2022. Rayyan was used to screen the retrieved literature risk of bias for included studies and was calculated using ROB2.0. The RevMan 5.3 software was used for the meta-analysis with the standard mean difference (SMD) and 95% confidence interval (CI). The model type was a random effect model, The risk ratio (RR) was used as the effect size for the two categorical variables. The swallowing function scores, withdrawal rate of nasal feeding tubes, and Length of stay (LOS) of the intervention and control groups were extracted, and the results of the meta-analysis were presented using a forest plot. Six studies from 2010 to 2018 with a total of 341 people were included in the meta-analysis. All studies reported quantitative outcome measures for the severity of dysphagia, and some reported the withdrawal rate of nasal feeding tubes, LOS, and penetration-aspiration-scale (PAS). The overall swallowing function of the PCES group was better than that of the control group (SMD = - 0.20, 95%CI - 0.38 to - 0.03, P = 0.02). In terms of the severity of dysphagia, there was a statistically significant difference in the Dysphagia Severity Rating scale (DSRS) between the Pharyngeal cavity electrical stimulation (PCES) group and the control group (SMD = - 0.24, 95%CI - 0.48 to 0, P = 0.05). The PCES group nasal feeding withdrawal rate of nasal feeding tubes was higher than the control group (RR = 2.88, 95% CI 1.15 to 7.26, P = 0.02). There was no significant difference in the LOS between the PCES group and the control group (SMD = - 0.19, 95%CI - 0.44 to 0.07, P = 0.15). This systematic review and meta-analysis provide reasonably reliable evidence that PCES-assisted swallowing can improve nasogastric feeding swallowing function and the withdrawal rate of nasal feeding tubes in patients with post-stroke dysphagia. However, the evidence for reducing oral feeding, aspiration, and length of hospitalization stay is lacking, and further studies are needed.

Planovalgus Foot Deformity in Patients Undergoing Total Hip Arthroplasty Is Associated With Increased Risk of Falls, Implant-Related Complications, and Revisions: A Case-Control Analysis.

BACKGROUND: Pes planus occurs due to the loss of the longitudinal arch of the foot, resulting in altered gait mechanics. This may lead to increased complications following total hip arthroplasty (THA). Thus, the aim of this study was to assess the effects that pes planus has on rates of falls, implant complications, fall-related injuries, and times to revision among THA patients. METHODS: A retrospective review of a private insurance claims database was conducted from 2010 to 2021. Patients who had a diagnosis of congenital or acquired pes planus and cases of THA were identified. Patients undergoing THA with a diagnosis of pes planus were matched to control patients 1:5 based on age, sex, and comorbidity profiles. Logistic regression was utilized to assess for differences in complication rates. RESULTS: A total of 3,622 pes planus patients were matched to 18,094 control patients. The pes planus group had significantly higher rates of falls than the control group (6.93 versus 2.97%, OR [odds ratio]: 2.43; CI [confidence interval]: 2.09 to 2.84; P < .001). Pes planus patients also had significantly greater odds of dislocation (OR: 1.89; CI: 1.58 to 2.27; P < .001), mechanical loosening (OR: 2.43; CI: 2.09 to 2.84; P = .019), and periprosthetic fracture (OR: 2.43; CI: 2.09 to 2.84; P < .001). The pes planus group had significantly greater rates of proximal humerus fractures (P = .008), but no difference was seen in distal radius fractures (P = .102). The time to revision was significantly shorter in the pes planus group (190 versus 554 days, P < .001). CONCLUSIONS: Pes planus in patients undergoing THA is associated with increased risk of complications and faster time to revision. These findings may allow orthopaedic surgeons to identify those patients at risk and allow for more educated patient counseling and operative planning.

Treating symptomatic flexible flatfoot deformities. a novel technique: comparison of uc berkeley laboratory foot orthosis with and without kinesio taping in juvenil athletes.

PURPOSE: Symptomatic flexible pes planus (SFPP) can cause pain and discomfort when walking or engaging in sportive activities in children and adolescents. SFPP can be treated conservatively with foot orthoses, such as the University of California Berkeley Laboratory (UCBL) foot orthosis, which can improve foot function and reduce pain. Kinesio Tape (KT) has also been used as an adjunct to foot orthoses in the treatment of pes planus. This study aims to compare the effectiveness of the UCBL foot orthosis with and without KT in the treatment of SFPP among amateur juvenile and adolescent athletes. METHODS: Fifty patients with SFPP were included in the study. In 27 patients UCBL foot orthosis with KT (group 1) was used whereas in 23 UCBL (group 2) was preferred only. The patients were evaluated with AOFAS and radiological measurements. RESULTS: The mean follow-up period was 28.6 ± 4.3(26) months. At the final follow-up AOFAS of group 1 was significantly higher than group 2. In group 2, 12 patients (%52,17) had pressure sores that caused superficial dermabrasion. Lateral TFMAs and talocalcaneal angle in group 1 was significantly better than group 2. CONCLUSIONS: This study attempted to determine if using KT with the UCBL foot orthosis was beneficial to the treatment of SFPP compared to simply wearing the orthosis. Our results suggest that KT is effective in reducing pronation and improving the AOFAS score. The use of UCBL with KT seems to be preferable in children and adolescents with SFPP since it is associated with a lower rate of complication, a higher degree of patient compliance and faster improvement in the radiological and clinical findings, compared to the use of the UCBL orthosis alone.

Validation of the pink esthetic score/white esthetic score at single tooth-supported prostheses in the esthetic zone: A randomized clinical trial.

OBJECTIVES: To validate the reproducibility and inter/intra-observer variability of the Pink Esthetic Score/White Esthetic Score (PES/WES) of single tooth-supported prostheses in the maxillary esthetic zone (13-23). MATERIALS AND METHODS: Forty-five patients were randomly assigned to one of the three treatment options (15 patients per group) receiving each one a different crown type: Porcelain fused to metal (PFM), monolithic zirconia, and lithium disilicate. Eight observers from each of four different specialties (Prosthodontists, Orthodontists, Periodontists, and Oral Surgeons) were recruited and assessed twice and four weeks apart (i.e., T1 and T2) 45 photographs of the single tooth-supported prosthesis using PES/WES and compared them with contralateral teeth. RESULTS: According to the ANOVA and post hoc tests, the zirconia crown type obtained the highest mean score by all observers, with a mean value of 16.70 ± 2.94. The prosthodontists and oral surgeons assigned the lowest mean score to PFM crowns, 13.03 ± 3.47 and 13.80 ± 3.17, respectively. Notably, the prosthodontists awarded the highest scores, specifically 17.50 ± 2.81 for the zirconia crowns. Intraobserver agreement was calculated utilizing the paired t-test. Pairwise comparisons between observers of different specialties revealed significant intraobserver agreement. Interclass correlation coefficient (ICC) scores were statistically significant among four specialties. No difference was detected concerning the interobserver agreement. CONCLUSIONS: The PES/WES index remains consistent across various observers from different specializations, yielding uniform results in the overall esthetic evaluation. Consequently, in light of the presented preliminary positive results, its use might also be considered for the esthetic assessment of single-tooth-supported prostheses. CLINICAL SIGNIFICANCE: The PES/WES index may be employed clinically to evaluate single tooth-supported prostheses as it emerged as a reproducible esthetic scoring system.

Outcomes of the "Calcaneo-stop" procedure for treating symptomatic flexible flatfoot in children: A systematic review and meta-analysis of 2394 feet.

BACKGROUND: This study evaluates the efficacy of the calcaneo-stop (C-Stop) procedure's effectiveness in treating symptomatic flexible flatfoot (FFF) in children. METHODS: A systematic review and meta-analysis were conducted using PubMed, Embase, and Cochrane databases to identify studies until 2023 on the outcomes of the C-Stop procedure in children with FFF. The risk of bias was assessed using MINORS criteria. RESULTS: Of 85 studies screened, 20 involving 2394 feet from 1415 patients (mean age 11.2 ± 1.3 years) were included. Post-procedure, significant improvements were noted in pain reduction (93.5%), heel alignment (95.21%), and radiological measures, including reductions in Kite (7.32º), Meary (11.65º), Costa-Bartani angles (17.11º), talar declination (12.63º) and increase in Calcaneal Pitch Angle (5.92º). AOFAS scores increased by 22.32 points on average, with 94.83% reporting high satisfaction. Complication rate was low (7.8%). CONCLUSIONS: The C-Stop procedure is effective for treating FFF in children, offering significant clinical, radiological, and functional improvements with high patient satisfaction and a low complication rate. LEVEL OF EVIDENCE: Level IV, Systematic review of Level-IV studies.

Alteration of the calf strength by heel cord lengthening, gastrocnemius recession through tenotomy or fasciotomy. A retrospective clinical force analysis before and after surgery.

BACKGROUND: Indications for surgical corrections about the Achilles tendon are increasing as additional measures in reconstructive interventions about the foot. These indications include shortened gastrocnemii, which cause a so-called 'functional pes equinus' and secondary forefoot imbalances, as well as corrections of pes planus and cavus. Surgery about the heel cord may also be indicated for achillodynia and diabetic pressure ulcers. However, there is a lack of evidence that quantifies the results of lengthening procedures about the heel cord. The aim of this study was to quantify the exact changes in calf strength one year after elongating the triceps surae, by measuring flexion forces in 90 degrees knee flexion and knee extension. METHODS: This study involves 69 patients who were examined for calf strength preoperatively and 1 year after gastrocnemius release. A new device, the Leonardo Mechanograph® (Novotec Medical) was used to measure calf strength. Measurements were performed with the knee flexed and extended. RESULTS: The operated leg had an overall statistically significant reduction in strength after surgery. Changes were similar on the contralateral leg. The difference in force reduction between the operated and non-operated leg was not statistically significant CONCLUSION: A correlation between measured plantar flexion forces of the foot after a reconstructive foot operation with or without a lengthening procedure about the calf musculature could not be established. LEVEL OF EVIDENCE: Level III: retrospective cohort study.

Effect of sequential burr passes on minimally invasive akin and first metatarsal dorsiflexion osteotomies.

BACKGROUND: Minimally invasive surgical (MIS) osteotomies are increasing as a surgical option for treating midfoot and forefoot conditions. This study aimed to evaluate the impact of each burr pass on the degree of correction, gap size, and alignment in MIS Akin and first metatarsal dorsiflexion osteotomies (DFO). METHODS: MIS Akin and first metatarsal DFO were performed on ten cadaveric specimens. Fluoroscopic measurements included the metatarsal dorsiflexion angle (MDA), dorsal cortical length (MDCL), first phalangeal medial cortical length (PCML) and proximal to distal phalangeal articular angle (PDPAA). RESULTS: The average decrease in PCML with each burr pass was as follows: 1.53, 1.33, 1.27, 1.23 and 1.13 mm at the 1st to 5th pass, respectively. The MDCL sequentially decreased by 1.80, 1.59, 1.35, 0.75, and 0.60 mm. The MDA consistently decreased, and the PDPAA incrementally became more valgus oriented. CONCLUSION: On average, a first metatarsal dorsal wedge resection of 4.7 mm and first phalangeal medial wedge resection of 2.9 mm was achieved after 3 and 2 burr passes, respectively. This data may aid surgeons determine the optimal number of burr passes required to achieve the desired patient-specific surgical correction.

Does pes anserinus tenotomy affect surgical site infection rate in operative tibial plateau fractures?

PURPOSE: To assess if pes anserinus tenotomy (PAT) during definitive open reduction and internal fixation (ORIF) of tibial plateau fractures is associated with a decreased risk of surgical site infection (SSI) and other postoperative complications. METHODS: A retrospective review of all adults who underwent ORIF for tibial plateau fractures from April 2005 to February 2022 at single level 1 trauma center was performed. Patients who had a medial approach to the plateau with minimum three-month follow-up were required for inclusion. All patients with fasciotomy for compartment syndrome or with traumatically avulsed or damaged pes anserinus prior to ORIF were excluded. Two groups were created: those who received a pes anserinus tenotomy with repair (PAT group) and those whose pes anserinus were spared and left intact (control group). Patient demographics, injury and operative characteristics, and surgical outcomes were compared. The primary outcomes were rates of deep and superficial SSI. RESULTS: The PAT group had significantly lower rates of deep SSI (9.2% vs. 19.7%, P = 0.009), superficial SSI (14.2% vs. 26.5%), P = 0.007), and any SSI (15.8% vs. 28.9%, P = 0.005). Multiple logistic regression showed that heart failure (aOR = 7.215, 95% CI 2.291-22.719, P < 0.001), and presence of open fracture (aOR = 4.046, 95% CI 2.074-7.895, P < 0.001) were independently associated with increased odds of deep SSI, while PAT was associated with a decreased odds of deep SSI (aOR = 0.481, 95% CI 0.231-0.992, P = 0.048). PAT had significantly lower rates of unplanned return to the operating room (20.8% vs. 33.7%, P = 0.010) and implant removal (10.0% vs. 18.0%, P = 0.042). CONCLUSION: While these data do not allow for discussion of functional recovery or strength, pes anserinus tenotomy was independently associated with significantly lower rates of infection, unplanned operation, and implant removal. LEVEL OF EVIDENCE: Level III.

Clinical outcomes of subtalar arthroereisis for the treatment of stage 1 flexible progressive collapsing foot deformity.

BACKGROUND: The use of subtalar arthroereisis as an adjunct to the surgical treatment of stage 1 flexible progressive collapsing foot deformity (PCFD) is controversial. The aim was to investigate the clinical outcomes and report the implant removal rate of subtalar arthroereisis as an adjunct for stage 1 PCFD. METHODS: A retrospective study of 212 consecutive feet undergoing operative management of stage 1 PCFD with adjunctive subtalar arthroereisis between October 2010 and April 2018. The primary outcome was the Foot and Ankle Outcome Score (FAOS). Secondary outcomes included Foot and Ankle Disability Index (FADI), Euroqol-5D-5L Index and implant removal rate. RESULTS: Post-operative clinical FAOS outcomes were collected for 153 feet (72.2%). At mean 2.5-year follow-up, the mean ± standard deviation FAOS for each domain was as follows; Pain: 81.5 ± 18.5, Symptoms: 79.5 ± 12.9, Activities of Daily Living: 82.5 ± 15.4 and Quality of Life: 64.2 ± 23.7. EQ-5D-5L Index was 0.884 ± 0.152. Pre-operative scores were available for 20 of these feet demonstrating a statistically significant improvement in all FAOS, FADI and EQ-5D-5L domains (p < 0.05). The implant removal rate for persistent sinus tarsi pain was 48.1% (n = 102). CONCLUSION: Use of a subtalar arthroereisis implant as an adjunct to conventional procedures in stage 1 flexible PCFD can result in significant improvement in pain and function. Patients should be counselled as to the relatively frequent rate of subsequent implant removal. LEVEL OF EVIDENCE: IV.

A ketogenic diet improves vascular hyperpermeability in type 2 diabetic mice by downregulating vascular pescadillo1 expression.

The role of pescadillo1 (PES1) in regulating vascular permeability has been unknown. This study probes the role of PES1 and its mediated molecular mechanism in modulating vascular hyperpermeability in diabetic mice. Male C57BL/6J and db/db mice were fed a standard diet and a ketogenic diet (KD). Meanwhile, mouse vascular endothelial cells (MVECs) were treated with ß-hydroxybutyric acid (ß-HB), Pes1 siRNA or a Pes1 overexpression plasmid. Additionally, knockout (KO) of Pes1 in mice was applied. After 12 weeks of feedings, enhanced vascular PES1 expression in diabetic mice was inhibited by the KD. The suppression of PES1 was also observed in ß-HB-treated MVECs. In mice with Pes1 KO, the levels of vascular VEGF and PES1 were attenuated, while the levels of vascular VE-cadherin, Ang-1 and Occludin were upregulated. Similar outcomes also occurred after the knockdown of Pes1 in cultured MVECs, which were opposite to the effects induced by PES1 overexpression in MVECs. In vitro and in vivo experiments showed that high glucose concentration-induced increases in vascular paracellular permeability declined after MVECs were treated by ß-HB or by knockdown of Pes1. In contrast, increases in vascular permeability were induced by overexpression of Pes1, which were suppressed by coadministration of ß-HB in cultured endothelial cells. Similarly declines in vascular permeability were found by Pes1 knockdown in diabetic mice. Mechanistically, ß-HB decreased PES1-facilitated ubiquitination of VE-cadherin. The KD suppressed the diabetes-induced increase in PES1, which may result in vascular hyperpermeability through ubiquitination of VE-cadherin in type 2 diabetic mice.

A mechanistic insight for the biosynthesis of N,N-dimethyltryptamine: An ONIOM theoretical approach.

Psychoactive natural products are potent serotonergic agonists capable of modulating brain functions such as memory and cognition. These substances have shown therapeutic potential for treating various mental disorders. The fact that N,N-dimethyltryptamine (DMT) is produced endogenously in several plants and animals, including humans, makes it particularly attractive. As an amino acid-derived alkaloid, the DMT biosynthetic pathway is part of the L-tryptophan biochemical cascade and can be divided into the decarboxylation by an aromatic L-amino acid decarboxylase (AADC) for tryptamine formation and the subsequent double-methylation by the indolethylamine-N-methyltransferase (INMT) through the cofactor S-adenosyl-L-methionine (SAM), a methyl donor. Unlike the decarboxylation mechanism of L-tryptophan, the molecular details of the double methylation of tryptamine have not been elucidated. Therefore, we propose an in silico model using molecular dynamics (MD), non-covalent interaction index (NCI) and density functional theory (DFT) calculations with the ONIOM QM:MM B3LYP/6-31+G(d,p):MM/UFF level of theory. Based on the obtained energetic data, the potential energy surface (PES) indicates an SN2 mechanism profile, with the second methylation energy barrier being the rate-limiting step with δG‡=60kJ∙mol-1 larger than the previous methylation, following the NCI analysis showing more repulsive interactions for the second transition state. In addition, the hybridization information of each reaction step provides geometric details about the double-methylation.

A UV-Reflective Organic-Inorganic Tandem Structure for Efficient and Durable Daytime Radiative Cooling in Harsh Climates.

Radiative cooling shows great promise in eco-friendly space cooling due to its zero-energy consumption. For subambient cooling in hot humid subtropical/tropical climates, achieving ultrahigh solar reflectance (≥96%), durable ultraviolet (UV) resistance, and surface superhydrophobicity simultaneously is critical, which, however, is challenging for most state-of-the-art scalable polymer-based coolers. Here an organic-inorganic tandem structure is reported to address this challenge, which comprises a bottom high-refractive-index polyethersulfone (PES) cooling layer with bimodal honeycomb pores, an alumina (Al2 O3 ) nanoparticle UV reflecting layer with superhydrophobicity, and a middle UV absorption layer of titanium dioxide (TiO2 ) nanoparticles, thus providing thorough protection from UV and self-cleaning capability together with outstanding cooling performance. The PES-TiO2 -Al2 O3 cooler demonstrates a record-high solar reflectance of over 0.97 and high mid-infrared emissivity of 0.92, which can maintain their optical properties intact even after equivalent 280-day UV exposure despite the UV-sensitivity of PES. This cooler achieves a subambient cooling temperature up to 3 °C at summer noontime and 5 °C at autumn noontime without solar shading or convection cover in a subtropical coastal city, Hong Kong. This tandem structure can be extended to other polymer-based designs, offering a UV-resist but reliable radiative cooling solution in hot humid climates.

PES1 reduces CD8+ T cell infiltration and immunotherapy sensitivity via interrupting ILF3-IL15 complex in esophageal squamous cell carcinoma.

BACKGROUND: Although immune checkpoint blockade (ICB) therapy has brought survival benefits to patients with specific cancer types, most of cancer patients remain refractory to the ICB therapy, which is largely attributed to the immunosuppressive tumor microenvironment. Thereby, it is urgent to profile key molecules and signal pathways responsible for modification of tumor microenvironment. METHODS: Multiple databases of esophageal squamous cell carcinoma (ESCC) were integratively analyzed to screen candidate genes responsible for infiltration of CD8+ T cells. Expression of pescadillo ribosomal biogenesis factor 1 (PES1) in clinical ESCC samples was examined by qRT-PCR, western blotting, and immunohistochemistry. The mechanisms of PES1 were investigated via RNA sequencing and mass spectrometry followed by immunoprecipitation and proximity ligation assay. The clinical and therapeutic significance of PES1 in ESCC was comprehensively investigated using ESCC cells and mouse model. RESULTS: PES1 was significantly upregulated and correlated with poor prognosis in ESCC patients. PES1 knockdown decreased ESCC cell growth in vitro and in vivo and enhanced the efficacy of ICB therapy in mouse model, which was established through subcutaneous inoculation with ESCC cells. Analyses on RNA sequencing and mass spectrometry suggested that PES1 expression was negatively correlated with IL15 and ILF3 was one of the PES1-associated proteins. It has been known that ILF3 interacts with and stabilizes IL15 mRNA to increase IL15 protein level. Our data further indicated that PES1 interfered with the interaction between ILF3 and IL15 mRNA and impaired ILF3-mediated stabilization of IL15 mRNA, which eventually reduced the protein level of IL15. Interestingly, the inhibitory effect of ICB therapy boosted by PES1 knockdown dramatically antagonized by knockdown of IL15, which suppressed the tumor-infiltrated CD8+ T cells in ESCC. Finally, we confirmed the relationships among PES1, IL15, and CD8+ T cell infiltration in 10 locally advanced ESCC patients receiving ICB neoadjuvant therapy and demonstrated that ICB therapy would be more effective in those with low expression of PES1. CONCLUSIONS: Altogether, our findings herein provided novel insights on biological function and clinical significance of PES1 and suggested that high expression of PES1 could suppress ILF3-IL15 axis-mediated immunosurveillance and promote resistance to ICB through restraining tumor-infiltrated CD8+ T cells.

Trihydrogen Cation Helium Clusters: A New Potential Energy Surface.

We present a new analytical potential energy surface (PES) for the interaction between the trihydrogen cation and a He atom, H 3 + - H e ${{H}_{3}^{+}-He}$ , in its electronic ground state. The proposed PES has been built as a sum of two contributions: a polarization energy term due to the electric field generated by the molecular cation at the position of the polarizable He atom, and an exchange-repulsion and dispersion interactions represented by a sum of "atom-bond" potentials between the three bonds of H 3 + ${{H}_{3}^{+}}$ and the He atom. All parameters of this new PES have been chosen and fitted from data obtained from high-level ab-initio calculations. Using this new PES plus the Aziz-Slaman potential for the interaction between Helium atoms and assuming pair-wise interactions, we carry out classical Basin-Hopping (BH) global optimization, semiclassical BH with Zero Point Energy corrections, and quantum Diffusion Monte Carlo simulations. We have found the minimum energy configurations of small He clusters doped with H 3 + ${{H}_{3}^{+}}$ , H 3 + H e N ${{H}_{3}^{+}{\left(He\right)}_{N}}$ , with N=1-16. The study of the energies of these clusters allows us to find a pronounced anomaly for N=12, in perfect agreement with previous experimental findings, which we relate to a greater relative stability of this aggregate.

Diagnostic efficacy of posterior tibialis tendon dysfunction: a systematic review of literature.

OBJECTIVE: To perform a systematic review to examine the diagnostic accuracy of magnetic resonance imaging, ultrasonography, and radiography in the evaluation of posterior tibial tendon dysfunction (PTTD). MATERIALS AND METHODS: Medline, Scopus, Embase, and The Cochrane Central Register of Controlled Trials (CENTRAL) were searched for relevant studies through April 2023. The study quality was assessed using the QUADAS-2 scoring system. RESULTS: Of the initial 634 studies, 12 studies met the quality criteria and were included, with 645 PTTs evaluated with MRI, 133 with US, and 97 with radiography. MRI was found to be more sensitive and specific than ultrasound, radiography, and clinical evaluation for detecting PTTD, with a sensitivity of up to 95%, specificity of up to 100%, and accuracy of 96% for detecting PTT tears. US showed a sensitivity of 80% and specificity of 90% for diagnosing tendinopathy, and a sensitivity of 90% and specificity of 80% for diagnosing peritendinosis when compared to MRI. Weight-bearing radiographs had a sensitivity of 71.4%, specificity of 88.9%, and diagnostic accuracy of 81.3% when diagnosing PTT ruptures. Various radiologic measurements were also found to have a significant relationship with PTT tears but were poorly correlated with PTT tendinosis and isolated tenosynovitis. CONCLUSION: Magnetic resonance imaging is the preferred imaging tool for evaluating patients with posterior tibial tendon dysfunction, with higher diagnostic accuracy, sensitivity, and specificity compared to ultrasound and radiographic imaging. However, initial imaging with ultrasound and radiographs may be used due to their availability and cost-effectiveness. CLINICAL RELEVANCE: PTTD affects 3% of women ≥ 40 years and 10% of adults ≥ 65 years globally. Using the appropriate imaging study, MRI ensures that patients suffering from PTTD are diagnosed and treated in a timely manner. KEY POINTS: • This review aimed to determine the diagnostic accuracy of MRI, ultrasonography, and radiography in evaluating PTTD. • MRI outperformed ultrasound and radiography, with higher sensitivity, specificity, and accuracy in detecting PTT tears. • MRI is the preferred imaging modality for the initial diagnosis of PTTD.