Structures of HCMV Trimer reveal the basis for receptor recognition and cell entry.

Human cytomegalovirus (HCMV) infects the majority of the human population and represents the leading viral cause of congenital birth defects. HCMV utilizes the glycoproteins gHgLgO (Trimer) to bind to platelet-derived growth factor receptor alpha (PDGFRα) and transforming growth factor beta receptor 3 (TGFßR3) to gain entry into multiple cell types. This complex is targeted by potent neutralizing antibodies and represents an important candidate for therapeutics against HCMV. Here, we determine three cryogenic electron microscopy (cryo-EM) structures of the trimer and the details of its interactions with four binding partners: the receptor proteins PDGFRα and TGFßR3 as well as two broadly neutralizing antibodies. Trimer binding to PDGFRα and TGFßR3 is mutually exclusive, suggesting that they function as independent entry receptors. In addition, Trimer-PDGFRα interaction has an inhibitory effect on PDGFRα signaling. Our results provide a framework for understanding HCMV receptor engagement, neutralization, and the development of anti-viral strategies against HCMV.

Oligoadenylate-Synthetase-Family Protein OASL Inhibits Activity of the DNA Sensor cGAS during DNA Virus Infection to Limit Interferon Production.

Interferon-inducible human oligoadenylate synthetase-like (OASL) and its mouse ortholog, Oasl2, enhance RNA-sensor RIG-I-mediated type I interferon (IFN) induction and inhibit RNA virus replication. Here, we show that OASL and Oasl2 have the opposite effect in the context of DNA virus infection. In Oasl2-/- mice and OASL-deficient human cells, DNA viruses such as vaccinia, herpes simplex, and adenovirus induced increased IFN production, which resulted in reduced virus replication and pathology. Correspondingly, ectopic expression of OASL in human cells inhibited IFN induction through the cGAS-STING DNA-sensing pathway. cGAS was necessary for the reduced DNA virus replication observed in OASL-deficient cells. OASL directly and specifically bound to cGAS independently of double-stranded DNA, resulting in a non-competitive inhibition of the second messenger cyclic GMP-AMP production. Our findings define distinct mechanisms by which OASL differentially regulates host IFN responses during RNA and DNA virus infection and identify OASL as a negative-feedback regulator of cGAS.

Structural architecture of the human NALCN channelosome.

Depolarizing sodium (Na+) leak currents carried by the NALCN channel regulate the resting membrane potential of many neurons to modulate respiration, circadian rhythm, locomotion and pain sensitivity1-8. NALCN requires FAM155A, UNC79 and UNC80 to function, but the role of these auxiliary subunits is not understood3,7,9-12. NALCN, UNC79 and UNC80 are essential in rodents2,9,13, and mutations in human NALCN and UNC80 cause severe developmental and neurological disease14,15. Here we determined the structure of the NALCN channelosome, an approximately 1-MDa complex, as fundamental aspects about the composition, assembly and gating of this channelosome remain obscure. UNC79 and UNC80 are massive HEAT-repeat proteins that form an intertwined anti-parallel superhelical assembly, which docks intracellularly onto the NALCN-FAM155A pore-forming subcomplex. Calmodulin copurifies bound to the carboxy-terminal domain of NALCN, identifying this region as a putative modulatory hub. Single-channel analyses uncovered a low open probability for the wild-type complex, highlighting the tightly closed S6 gate in the structure, and providing a basis to interpret the altered gating properties of disease-causing variants. Key constraints between the UNC79-UNC80 subcomplex and the NALCN DI-DII and DII-DIII linkers were identified, leading to a model of channelosome gating. Our results provide a structural blueprint to understand the physiology of the NALCN channelosome and a template for drug discovery to modulate the resting membrane potential.

Evaluation of antihypertensive activity and molecular docking analysis of Padina boergesenii extract.

INTRODUCTION: Antihypertensive drugs that are chemically synthesized usually tend to initiate different health complications. The quest for bioactive molecules to create novel medicines has focused on Marine resources like seaweeds. These molecules can furnish a positive probability for patients to gain benefits from these natural substances. METHODS: This study aims to identify phytoconstituents present in brown seaweed-Padina boergesenii. Five different solvents were used to prepare extracts and their antioxidant activity as well as antihypertensive activity was evaluated. Phytoconstituents were identified using LC-MS/MS, and subjected to molecular interaction against ACE enzyme. RESULTS: The 70% ethanolic extract exhibited the highest total phenolic content (TPC), significant radical scavenging activity and concentration dependent Angiotensin Converting Enzyme (ACE) inhibition activity. LC-MS/MS analysis confirmed the presence of bioactive compounds from which 7,8 dihydroxycoumarin had the highest affinity against ACE enzyme in molecular docking study. CONCLUSION: These findings advocate that Padina boergesenii can be a potential source for developing novel antihypertensive therapeutic drug(s) and could pave the way for evolving effective and safe remedies from natural resources.

The anesthetic management of a child with ohtahara syndrome and severe stridor: a case report.

BACKGROUND: Ohtahara syndrome is a progressive developmental and epileptic encephalopathy that manifests in the early infantile period. This rare condition is characterized by intractable seizures, psychomotor retardation, and poor prognosis. To date, there are a handful of case reports regarding the anesthetic management of children with Ohtahara syndrome. However, limited reports exist of patients with Ohtahara syndrome who present with difficult airways. This report describes our airway findings and general anesthetic management of a pediatric patient with Ohtahara syndrome undergoing diagnostic bronchoscopy for severe inspiratory stridor. CASE PRESENTATION: A 14-month-old, 9 kg, male patient with Ohtahara syndrome presented with a year-long history of severe inspiratory stridor and was scheduled for bronchoscopy with lavage. On exam, the patient had noisy breathing, was non-verbal with developmental delay, and had poor head control with significant central hypotonia. The patient was induced with ketamine and general anesthesia was maintained with propofol. Bronchoscopic evaluation was completed uneventfully and revealed a diagnosis of laryngotracheomalacia. The patient's breathing was maintained spontaneously throughout the procedure and no seizures were noted. In the post anesthesia care unit, the patient's respiratory and cardiovascular function were stable. CONCLUSIONS: This report documents the unusual finding of severe inspiratory stridor in a 14-month-old child diagnosed with Ohtahara syndrome and our anesthetic management during their diagnostic bronchoscopy. Currently, documentation of complex airway pathology present in patients with Ohtahara syndrome is limited and should be further evaluated. This will assist pediatric anesthesiologists as these patients may require careful preoperative assessment, thoughtful airway management, and surgical alternatives on standby.

Optic Nerve Sheath Diameter is not a predictor of functional outcomes in ICH Patients.

OBJECTIVES: Optic nerve sheath diameter (ONSD) may serve as an early marker of increasing intracranial pressure resulting from intracerebral hemorrhage (ICH). We investigated if changes in ONSD can predict 90-day functional outcomes in ICH patients. MATERIALS AND METHODS: We utilized ERICH (Ethnic/Racial Variations of Intracerebral Hemorrhage), a prospective, multi-center, case-control study of 3000 patients. We included patients with baseline and follow-up head CT with available outcomes. We measured change in ONSD from baseline and follow-up CT within a 6 (±1) hour window. Our primary outcome was the 90-day Modified Rankin (mRS) score. We compared patients with good (mRS 0-3) versus poor outcomes (mRS 4-6) to presence of significant change in ONSD using univariate analysis. We did an analysis of variance to assess for differences in ONSD. RESULTS: Of 93 ICH patients who fit the inclusion criteria, the mean age was 64.1 (SD +/- 14.6), with 36.6 % being females. Forty-nine patients (47.1 %) had significant ONSD change between baseline and follow-up CT. ONSD change in the poor outcome group was not significantly different than that of the good outcome group in both the right and left hemispheres (p = 0.21 and p = 0.63 respectively). CONCLUSIONS: We found that early change in the ONSD within the first 6 h of presentation in patients with ICH does not predict functional outcomes at three months.

Atherosclerosis in Systemic Lupus Erythematosus.

PURPOSE OF THE REVIEW: Systemic lupus erythematosus (SLE) patients are at increased risk of cardiovascular disease (CVD) compared to the general population, despite most patients being young females, who are not classically considered to be at high risk for cardiovascular disease using traditional risk assessment tools. The purpose of this review is to discuss the pathophysiology of atherosclerosis in SLE and raise awareness of the relationship between SLE and CVD. RECENT FINDINGS: The increased risk of CVD in SLE patients is multifactorial, due to proatherogenic lipid profiles, immune dysregulation and inflammation, side effects of lupus treatment, and microvascular dysfunction. Conventional CV risk models often underperform in the identification of SLE patients at high risk of atherosclerosis. The use of non-invasive imaging serves as a strategy to identify patients with evidence of subclinical CVD and in the evaluation of symptomatic patients. Identification of subclinical atherosclerosis allows for aggressive management of CV risk factors. SLE patients experience an increased risk of atherosclerotic CVD, which is not solely explained by traditional CV risk factors. It is imperative that clinicians are aware of this association to implement prompt detection and treatment of atherosclerotic CVD in SLE patients.

Estimated sdLDL-C for predicting high-risk coronary plaque features in psoriasis: a prospective observational study.

BACKGROUND: Psoriasis (PSO) is a skin disorder with systemic inflammation and high coronary artery disease risk. A distinct lipid phenotype occurs in psoriasis, which is characterized by high plasma triglycerides (TGs) with typically normal or even low LDL-C. The extent to which cholesterol on LDL subfractions, such as small dense LDL-C (sdLDL-C), are associated with vulnerable coronary plaque characteristics in PSO remains elusive. METHODS: A recently developed equation for estimating sdLDL-C from the standard lipid panel was utilized in a PSO cohort (n = 200) with 4-year follow-up of 75 subjects. Coronary plaque burden was assessed by quantitative coronary computed tomography angiography (CCTA). Multivariate regression analyses were used for establishing associations and prognostic value of estimated sdLDL-C. RESULTS: Estimated sdLDL-C was positively associated with non-calcified burden (NCB) and fibro-fatty burden (FFB), which remained significant after multivariate adjustment for NCB (ß = 0.37; P = 0.050) and LDL-C adjustment for FFB (ß = 0.29; P < 0.0001). Of note, total LDL-C calculated by the Friedewald equation was not able to capture these associations in the study cohort. Moreover, in the regression modelling estimated sdLDL-C was significantly predicting necrotic burden progression over 4 years follow-up (P = 0.015), whereas LDL-C did not. Finally, small LDL particles (S-LDLP) and small HDL particles (S-HDLP), along with large and medium TG-rich lipoproteins (TRLPs) had the most significant positive correlation with estimated sdLDL-C. CONCLUSIONS: Estimated sdLDL-C has a stronger association than LDL-C with high-risk features of coronary atherosclerotic plaques in psoriasis patients. CLINICAL TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov . Unique identifiers: NCT01778569.

High-Density Lipoprotein Cholesterol in Atherosclerotic Cardiovascular Disease Risk Assessment: Exploring and Explaining the "U"-Shaped Curve.

PURPOSE OF REVIEW: Review updates for the association of HDL-cholesterol with atherosclerotic cardiovascular disease (ASCVD) and discuss the approach to incorporating HDL-cholesterol within risk assessment. RECENT FINDINGS: There is a U-shaped relationship between HDL-cholesterol and ASCVD. Both low HDL-cholesterol (< 40 mg/dL in men, < 50 mg/dL in women) and very-high HDL-cholesterol (≥ 80 mg/dL in men) are associated with a higher risk of all-cause and ASCVD mortality, independent from traditional risk factors. There has been inconsistency for the association between very-high HDL-cholesterol and mortality outcomes in women. It is uncertain whether HDL-cholesterol is a causal ASCVD risk factor, especially due to mixed results from Mendelian randomization studies and the collinearity of HDL-cholesterol with established risk factors, lifestyle behaviors, and socioeconomic status. HDL-cholesterol is a risk factor or risk enhancer in primary prevention and high-risk condition in secondary prevention when either low (men and women) or very-high (men). The contribution of HDL-cholesterol to ASCVD risk calculators should reflect its observed U-shaped association with all-cause and ASCVD mortality.

Promoting Publications Through Plastic Surgery Journal Instagram Accounts: Is It Worth It?

PURPOSE: Journals are increasingly using social media to increase article engagement. We aim to determine the impact of Instagram promotion on, and identify social media tools that effectively enhance, plastic surgery article engagement and impact. METHODS: Instagram accounts for Plastic and Reconstructive Surgery , Annals of Plastic Surgery , Aesthetic Surgery Journal , and Aesthetic Plastic Surgery were reviewed for posts published by February 8, 2022. Open access journal articles were excluded. Post caption word count and number of likes, tagged accounts, and hashtags were recorded. Inclusion of videos, article links, or author introductions was noted. All articles from journal issues published between the dates of the first and last posts promoting articles were reviewed. Altmetric data approximated article engagement. Citation numbers from the National Institutes of Health iCite tool approximated impact. Differences in engagement and impact of articles with and without Instagram promotion were compared by Mann-Whitney U tests. Univariate and multivariable regressions identified factors predictive of more engagement (Altmetric Attention Score, ≥5) and citations (≥7). RESULTS: A total of 5037 articles were included, with 675 (13.4%) promoted on Instagram. Of posts featuring articles, 274 (40.6%) included videos, 469 (69.5%) included article links, and 123 included (18.2%) author introductions. Promoted articles had higher median Altmetric Attention Scores and citations ( P < 0.001). On multivariable analysis, using more hashtags predicted higher article Altmetric Attention Scores (odds ratio [OR], 1.85; P = 0.002) and more citations (OR, 1.90; P < 0.001). Including article links (OR, 3.52; P < 0.001) and tagging more accounts (OR, 1.64; P = 0.022) predicted higher Altmetric Attention Scores. Including author introductions negatively predicted Altmetric Attention Scores (OR, 0.46; P < 0.001) and citations (OR, 0.65; P = 0.047). Caption word count had no significant impact on article engagement or impact. CONCLUSIONS: Instagram promotion increases plastic surgery article engagement and impact. Journals should use more hashtags, tag more accounts, and include manuscript links to increase article metrics. We recommend that authors promote on journal social media to maximize article reach, engagement, and citations, which positively impacts research productivity with minimal additional effort in designing Instagram content.

Genotypic analyses and antimicrobial resistance profiles of Campylobacter jejuni from crows (Corvidae) of United States and India reflect their respective local antibiotic burdens.

AIM: The study examined the hypothesis that crow-borne Campylobacter can function as environmental reservoirs and indicators of antibiotic resistance (AR) determinants circulating in a human population. METHODS AND RESULTS: Two species of crows from Washington (WA), United States, and Kolkata, India, respectively, were examined for their ability to carry antibiotic resistant Campylobacter. Campylobacter jejuni was the only species isolated by selective agar plating from crow faecal samples. Disk diffusion method used to compare the AR profile of the isolates showed tetracycline (TET) resistance to be the most prevalent (27%) among WA isolates, followed by ciprofloxacin (CIP; 24%). Among Kolkata isolates, nalidixic acid resistance was most common (36%), followed by CIP (27%). The AR profile demonstrated by crow isolates of WA reflects those reported by the US National Antimicrobial Resistance Monitoring System for human isolates (2007-2011), where resistance to TET was most prevalent (≈45%), followed by quinolones (≈24%). The Kolkata crow isolates reflected the AR profile of human clinical isolates from India, where 97% resistance was shown to quinolones, followed by TET (18%). Multilocus sequence typing of 37 isolates, including 11 water isolates from the crow roost area, showed 24 different sequence types (STs). Seventeen of these were previously found in wild birds, 2 in human diarrhoea, 4 in poultry and 8 in environmental water. One isolate was found in both water and faeces, though from different sites within WA. CONCLUSIONS: The results indicate that crows most likely acquire the AR from anthropogenic sources. Although they are colonized by specific STs, rarely isolated from humans, they can facilitate the spread of AR. SIGNIFICANCE AND IMPACT OF THE STUDY: By studying two areas in different continents, this research demonstrates that Campylobacter borne by crows can function as environmental reservoirs and indicators of AR determinants that circulate in a human population. This information will be of importance to scientists from the medical and poultry industries.

Distinct gut and vaginal microbiota profile in women with recurrent implantation failure and unexplained infertility.

BACKGROUND: Female reproductive tract dysbiosis impacts implantation. However, whether gut dysbiosis influences implantation failure and whether it accompanies reproductive tract dysbiosis remains scantly explored. Herein, we examined the gut-vaginal microbiota axis in infertile women. METHODS: We recruited 11 fertile women as the controls, and a cohort of 20 infertile women, 10 of whom had recurrent implantation failure (RIF), and another 10 had unexplained infertility (UE). Using amplicon sequencing, which employs PCR to create sequences of DNA called amplicon, we compared the diversity, structure, and composition of faecal and vaginal bacteria of the controls with that of the infertile cohort. Of note, we could only sequence 8 vaginal samples in each group (n = 24/31). RESULT: Compared with the controls, α-diversity and ß-diversity of the gut bacteria among the infertile groups differed significantly (p < 0.05). Taxa analysis revealed enrichment of Gram-positive bacteria in the RIF group, whereas Gram-negative bacteria were relatively abundant in the UE group. Strikingly, mucus-producing genera declined in the infertile cohort (p < 0.05). Hungatella, associated with trimethylamine N-oxide (TMAO) production, were enriched in the infertile cohort (p < 0.05). Vaginal microbiota was dominated by the genus Lactobacillus, with Lactobacillus iners AB-1 being the most abundant species across the groups. Compared with the infertile cohort, overgrowth of anaerobic bacteria, associated with vaginal dysbiosis, such as Leptotrichia and Snethia, occurred in the controls. CONCLUSION: The gut microbiota had little influence on the vaginal microbiota. Gut dysbiosis and vaginal eubiosis occurred in the infertile women, whereas the opposite trend occurred in the controls.

Rapid decomposition of rice straw by application of a novel microbial consortium and study its microbial community dynamics.

Rice straw decomposition is an attractive solution to open-field burning but the traditional method has slow kinetics and takes 60-90 days to obtain mature compost. In this study, we propose to boost up the decomposition process by addition of a novel microbial consortium rich in lignocellulolytic microbes. C: N ratio of the compost reached 11.69% and degradation efficiency of cellulose and hemicellulose was found to be 64 and 87% respectively within 25 days. Lignocellulolytic activity of the microbial consortium was confirmed by plate and activity assay. These parameters clearly indicated that a mature compost was obtained in 25 days. The 16S rRNA gene amplicon sequencing and functional analysis of predicted genes indicated amino acid and carbohydrate metabolism as the major metabolic pathway during composting. The tertiary level of functional analysis revealed the major metabolic pathways in the bacterial communities as pentose phosphate pathway, glycolysis and tricarboxylic acid cycle.

The application of molecular imaging to advance translational research in chronic inflammation.

Over the past several decades, molecular imaging techniques to assess cellular processes in vivo have been integral in advancing our understanding of disease pathogenesis. 18F-fluorodeoxyglucose (18-FDG) positron emission tomography (PET) imaging in particular has shaped the field of atherosclerosis research by highlighting the importance of underlying inflammatory processes that are responsible for driving disease progression. The ability to assess physiology using molecular imaging, combining it with anatomic delineation using cardiac coronary angiography (CCTA) and magnetic resonance imaging (MRI) and lab-based techniques, provides a powerful combination to advance both research and ultimately clinical care. In this review, we demonstrate how molecular imaging studies, specifically using 18-FDG PET, have revealed that early vascular disease is a systemic process with multiple, concurrent biological mechanisms using inflammatory diseases as a basis to understand early atherosclerotic mechanisms in humans.

Metabolic syndrome and its factors are associated with noncalcified coronary burden in psoriasis: An observational cohort study.

BACKGROUND: Psoriasis is associated with a heightened risk of cardiovascular disease and higher prevalence of metabolic syndrome. OBJECTIVE: Investigate the effect of metabolic syndrome and its factors on early coronary artery disease assessed as noncalcified coronary burden by coronary computed tomography angiography in psoriasis. METHODS: This cross-sectional study consisted of 260 participants with psoriasis and coronary computed tomography angiography characterization. Metabolic syndrome was defined according to the harmonized International Diabetes Federation criteria. RESULTS: Of the 260 participants, 80 had metabolic syndrome (31%). The metabolic syndrome group had a higher burden of cardiometabolic disease, systemic inflammation, noncalcified coronary burden, and high-risk coronary plaque. After adjusting for Framingham risk score, lipid-lowering therapy, and biologic use, metabolic syndrome (ß = .31; P < .001) and its individual factors of waist circumference (ß = .33; P < .001), triglyceride levels (ß = .17; P = .005), blood pressure (ß = .18; P = .005), and fasting glucose (ß = .17; P = .009) were significantly associated with noncalcified coronary burden. After adjusting for all other metabolic syndrome factors, blood pressure and waist circumference remained significantly associated with noncalcified coronary burden. LIMITATIONS: Observational nature with limited ability to control for confounders. CONCLUSIONS: In psoriasis, individuals with metabolic syndrome had more cardiovascular disease risk factors, systemic inflammation, and noncalcified coronary burden. Efforts to increase metabolic syndrome awareness in psoriasis should be undertaken to reduce the heightened cardiovascular disease risk.

Bio-prospecting the future in perspective of amidohydrolase L-glutaminase from marine habitats.

In the current scenario, considerable attention is being given to the enzyme L-glutaminase (EC 3.5.1.2). It belongs to the amidohydrolase class adherent to the family of serine-reliant ß-lactamases and the penicillin-binding proteins due to its higher affinity to polymerize and modify peptidoglycan synthesis. However, based on the catalytic proficiency, L-glutaminase is characterized as a proteolytic endopeptidase that cleaves peptide linkage and emancipates various byproducts, viz. ammonia along with glutamate. L-glutamine is considered the key amino acid reportedly involved in multiple metabolic pathways such as nitrogen metabolism. The present review is focused on the recent development and aspects concomitant to the biotechnological applicability of L-glutaminase predominantly from the marine habitat. Additionally, a majority of L-glutaminases finds application in cancer therapy as therapeutic agents, especially for acute lymphocytic leukaemia. The in vitro studies have been effective against various human cancer cell lines. L-glutaminase enhances the growth of probiotic bacteria. Apart from all these applications, it is suitably applicable in fermented foods as a flavour enhancer especially the umami flavour and content. Marine habitats have largely been exploited for their bio-catalytic potential but very scarcely for therapeutic enzymes. Some of the reports of such marine bacterial isolates from Bacillus sp., Pseudomonas sp. and Vibrio sp. are in the domain, but none highlights the therapeutic applications predominantly as anticancer and anti-proliferative agents. KEY POINTS: The exploration of marine habitats along the Gujarat coasts mainly for bacteria secreting L-glutaminase is scarcely reported, and even more scarce are the amidohydrolases from these marine niches as compared to their terrestrial counterparts. Microbial sourced amidohydrolase has wide bio-applicability that includes food, cosmetics and therapeutics especially as anticancer/anti-proliferative agent making it of immense biotechnological significance.

Post hoc assessment of the relationship among coronary stenosis, electrocardiography, and ventricular function in patients with heart disease.

Cardiovascular diseases including cardiac arrhythmias lead to fatal events in patients with coronary artery disease; however, clinical associations from echocardiography, electrocardiography (ECG), and biomarkers remain unknown. We sought to identify the factors that may be related to elevated QRS intervals in patients with risk for coronary artery disease. In this study, we performed analysis of clinical data from 503 patients divided into two groups, i.e., patients with either <50% coronary artery stenosis or >50% coronary artery stenosis. We further examined patients with elevated ECG parameters such as QRS > 100 ms and QTc > 440 ms. Patients with >50% coronary artery stenosis exhibited significant increases in age, triglycerides, and troponin levels. Further, ECG parameters demonstrated increased QRS and QTc durations, while echocardiographic parameters highlighted a decrease in ejection fraction (EF) and fractional shortening (FS). Patients with QTc > 440 ms exhibited increased brain natriuretic peptide and creatinine levels with a decrease in estimated glomerular filtration rate clearance rates. Patients with QRS > 100 ms had greater left ventricular (LV) mass and LV internal diameter in systole and diastole. Multimodal logistic regression showed significant relation between QTc, age, and creatinine. These findings suggest that patients with significant coronary stenosis may have lower EF and FS with prolonged QRS intervals, demonstrating greater risk for arrhythmic events.

Subcutaneous Delivery of Albumin: Impact of Thermosensitive Hydrogels.

Albumin demonstrates remarkable promises as a versatile carrier for therapeutic and diagnostic agents. However, noninvasive delivery of albumin-based therapeutics has been largely unexplored. In this study, injectable thermosensitive hydrogels were evaluated as sustained delivery systems for Cy5.5-labeled bovine serum albumin (BSA-Cy5.5). These hydrogels were prepared using aqueous solutions of Poloxamer 407 (P407) or poly(lactide-co-glycolide)-block-poly(ethylene glycol)-block-poly(lactide-co-glycolide) (PLGA-PEG-PLGA), which could undergo temperature-triggered phase transition and spontaneously solidify into hydrogels near body temperature, serving as in situ depot for tunable cargo release. In vitro, these hydrogels were found to release BSA-Cy5.5 in a sustained manner with the release half-life of BSA-Cy5.5 from P407 and PLGA-PEG-PLGA hydrogels at 16 h and 105 h, respectively. Without affecting the bioavailability, subcutaneous administration of BSA-Cy5.5-laden P407 hydrogel resulted in delayed BSA-Cy5.5 absorption, which reached the maximum plasma level (Tmax) at 24 h, whereas the Tmax for subcutaneously administered free BSA-Cy5.5 solution was 8 h. Unexpectedly, subcutaneously injected BSA-Cy5.5-laden PLGA-PEG-PLGA hydrogel did not yield sustained BSA-Cy5.5 plasma level, the bioavailability of which was significantly lower than that of P407 hydrogel (p < 0.05). The near-infrared imaging of BSA-Cy5.5-treated mice revealed that a notable portion of BSA-Cy5.5 remained trapped within the subcutaneous tissues after 6 days following the subcutaneous administration of free solution or hydrogels, suggesting the discontinuation of BSA-Cy5.5 absorption irrespective of the formulations. These results suggest the opportunities of developing injectable thermoresponsive hydrogel formulations for subcutaneous delivery of albumin-based therapeutics.

Accessing Highly Tunable Nanostructured Hydrogels in a Short Ionic Complementary Peptide Sequence via pH Trigger.

Creating diverse nanostructures from a single gelator through modulating the self-assembly pathway has been gaining much attention in recent years. To this direction, we are exploring the effect of modulation of pH as a potential self-assembly pathway in governing the physicochemical properties of the final gel phase material. In this context, we used a classical nongelator with the ionic complementary sequence FEFK, which was rationally conjugated to an aromatic group naphthoxyacetic acid (Nap) at the N-terminal end to tune its gelation behavior. Interestingly, the presence of oppositely charged amino acids in the peptide amphiphile resulted in pH-responsive behavior, leading to the formation of hydrogels over a wide pH range (2.0-12.0); however, their structures differ significantly at the nanoscale. Thus, by simply manipulating the overall charge over the exposed surface of the peptide amphiphiles as a function of pH, we were able to access diverse self-assembled nanostructures within a single gelator domain. The charged state of the gelator at the extreme pH (2.0, 12.0) led to a thinner fiber formation, in contrast to the thicker fibers observed near the physiological pH owing to charge neutralization, thus promoting the lateral association. Such variation in molecular packing was found to be further reflected in the variable mechanical strengths of the peptide hydrogels obtained at different pH values. Moreover, the gelation of the peptide at physiological pH offers an additional advantage to explore this hydrogel as a cell culture scaffold. We anticipate that our study on controlling the self-assembly pathway of the ionic complementary peptide amphiphile can be an elegant approach to access diverse self-assembled materials, which can expand the zone of its applicability as a stimuli-responsive biomaterial.

Stroke-like migraine attacks after radiation therapy (SMART) syndrome-a case series and review.

INTRODUCTION: Cranial irradiation is used both prophylactically and for the treatment of brain tumors. There are various complications associated with it. The rare complication of stroke-like migraine attacks after radiation therapy (SMART) syndrome usually occurs several years after radiation therapy but is a reversible phenomenon. It usually presents with headaches, seizures, or other focal neurological deficits concerning stroke or recurrence of the underlying disease. OBJECTIVES: We aim to present two cases of SMART syndrome highlighting the typical presentation, imaging findings, and differential diagnosis. We also conducted the literature review since the early recognition of this rare delayed onset complication is crucial, given its self-limited course and to avoid misinterpretations of the cases. CONCLUSION: Our extensive review favors MRI, CT, and prolonged EEG monitoring to rule out other differentials and showed that initiation of corticosteroid therapy and antiepileptic treatment were helpful in the resolution of symptoms and prevent recurrences. Therefore, future studies should be focused on early identification and management guidelines for SMART syndrome.