Morphological and molecular characterizations of Pratylenchus coffeae infecting Ming aralia and coffee in Vietnam.

Pratylenchus coffeae, belonging to the root-lesion nematode group, is a highly prevalent and destructive plant-parasitic nematode that is able to infest a wide range of host plants. Although this species' devastating impacts on coffee plantations across the world are widely known on other host plants, its association with Ming aralia has never been reported. Our study characterized two popu lations of P. coffeae (associated with Ming aralia and coffee) and compared them with other popu lations from previous studies in Vietnam and other countries in the world. The identification of P. coffeae in our study was confirmed by the comprehensive analysis encompassing morphological examination, morphometric data, and molecular characterizations of the COI mtDNA and D2D3 of 28S rRNA regions. The cluster and MDS analyses revealed that the two populations of P. coffeae from Vietnam are closely related to those from Japan and Indonesia. The D2-D3 sequences of 28S rRNA and COI mtDNA regions exhibited high similarity among these populations, indicating a stable genetic profile. Our research contributes to a better understanding of the distribution and genetic characterizations of P. coffeae by offering new morphological and molecular insights into the presence of this nematode in Vietnam. Additionally, this nematode species was found to be associated with host plant's symptoms such as chlorotic leaves, stunted growth and root lesion in both hosts. Given the economic significance of both Ming aralia and coffee crops in Vietnam, as well as the damaging potential of P. coffeae, this study emphasizes the need of proactive nematode management measures to control this destructive pest.

Management of ruptured aneurysmal subarachnoid hemorrhage with multiple basilar trunk aneurysms using a flow-diverter stent: A case report.

Ruptured aneurysmal subarachnoid hemorrhage associated with multiple basilar trunk aneurysms represents a rare clinical condition. Endovascular intervention stands as the preferred therapeutic approach. We present the case of a 35-year-old patient with subarachnoid hemorrhage and three consecutive basilar trunk aneurysms. Utilizing a flow-diverter stent, we achieved simultaneous occlusion of all 3 aneurysms, performed 2 hours post dual antiplatelet therapy (comprising salicylic acid 300 mg and ticagrelor 180 mg). Sustained resistance to clopidogrel necessitated the subsequent 3 months, followed by single antiplatelet therapy. At the 1-month follow-up, the patient demonstrated a favorable clinical course, devoid of cerebral infarction, and evidenced unobstructed stent patency upon brain magnetic resonance imaging.

Comprehensive analysis of the microbiome in Apis cerana honey highlights honey as a potential source for the isolation of beneficial bacterial strains.

Background: Honey is a nutritious food made by bees from nectar and sweet deposits of flowering plants and has been used for centuries as a natural remedy for wound healing and other bacterial infections due to its antibacterial properties. Honey contains a diverse community of bacteria, especially probiotic bacteria, that greatly affect the health of bees and their consumers. Therefore, understanding the microorganisms in honey can help to ensure the quality of honey and lead to the identification of potential probiotic bacteria. Methods: Herein, the bacteria community in honey produced by Apis cerana was investigated by applying the next-generation sequencing (NGS) method for the V3-V4 hypervariable regions of the bacterial 16S rRNA gene. In addition, lactic acid bacteria (LAB) in the honey sample were also isolated and screened for in vitro antimicrobial activity. Results: The results showed that the microbiota of A. cerana honey consisted of two major bacterial phyla, Firmicutes (50%; Clostridia, 48.2%) and Proteobacteria (49%; Gammaproteobacteria, 47.7%). Among the 67 identified bacterial genera, the three most predominant genera were beneficial obligate anaerobic bacteria, Lachnospiraceae (48.14%), followed by Gilliamella (26.80%), and Enterobacter (10.16%). Remarkably, among the identified LAB, Lactobacillus kunkeei was found to be the most abundant species. Interestingly, the isolated L. kunkeei strains exhibited antimicrobial activity against some pathogenic bacteria in honeybees, including Klebsiella spp., Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa and Staphylococcus aureus. This underscores the potential candidacy of L. kunkeei for developing probiotics for medical use. Taken together, our results provided new insights into the microbiota community in the A. cerana honey in Hanoi, Vietnam, highlighting evidence that honey can be an unexplored source for isolating bacterial strains with potential probiotic applications in honeybees and humans.

Quantitative assessment of molecular, microstructural, and macroscopic changes of red kidney beans (Phaseolus vulgaris L.) during cooking provides detailed insights in their cooking behavior.

Quantitative changes at different length scales (molecular, microscopic, and macroscopic levels) during cooking were evaluated to better understand the cooking behavior of common beans. The microstructural evolution of presoaked fresh and aged red kidney beans during cooking at 95 °C was quantified using light microscopy coupled with image analysis. These data were related to macroscopic properties, being hardness and volume changes representing texture and swelling of the beans during cooking. Microstructural properties included the cell area (Acell), the fraction of intercellular spaces (%Ais), and the fraction of starch area within the cells (%As/c), reflecting respectively cell expansion, cell separation, and starch swelling. A strong linear correlation between hardness and %Ais (r = -0.886, p = 0.07), along with a significant relative change in %Ais (∼5 times), suggests that softening is predominantly due to cell separation rather than cell expansion. Regarding volume changes, substantial cell expansion (Acell increased by ∼1.5 times) during the initial 30 min of cooking was greatly associated with the increase in the cotyledon volume, while the significance of cell separation became more prominent during the later stages of cooking. Furthermore, we found that the seed coat, rather than the cotyledon, played a major role in the swelling of whole beans, which became less pronounced after aging. The macroscopic properties did not correlate with %As/c. However, the evolution of %As/c conveyed information on the swelling of the starch granules during cooking. During the initial phase, the starch granule swelling mainly filled the cells, while during the later phase, the further swelling was confined by the cell wall. This study provides strong microscopic evidence supporting the direct involvement of the cell wall/ middle lamella network in microstructural changes during cooking as affected by aging, which is in line with the results of molecular changes.

Effects of adaptive duration to salinity in drinking water on behavior, weight gain and blood biochemical parameters in growing goats.

This experiment aimed to determine the effect of adaptive duration to saline water on behaviors, weight gain and blood biochemical parameters in growing goats. The experiment was arranged in a completely randomized design, which included four treatments with five animals per group. The goats were administered either fresh water (control) or seawater with a salinity of 1.5%, with varying durations of adaptation to seawater. The adaptive durations included an abrupt change (A0) from fresh water to seawater with a salinity of 1.5% or stepwise adaptation either 4 (A4) or 7 (A7) days of increasing saline concentrations. The results showed that dry matter intake in the non-adapted goats (A0 group) was lower than that of the control group or the adapted goats throughout the experiment (p<0.05). In contrast, water intake from drinking saline water was greater than that in the control group (p<0.05). Body weigh did not differ among the treatments; however, non-adapted goats exhibited a lower weight gain than the adapted goats (p<0.05). The goats in the A0 and A4 groups exhibited increased plasma levels of urea, AST, and ALT compared with the control and A7 groups. However, blood electrolyte levels remained unchanged and were within the normal range for goats. Therefore, it is concluded that the stepwise adaptation to seawater with a salinity of 1.5% for 21 days has no influence on productivity and health status of goats.

Comparing Intramedullary Nails and Locking Plates in Displaced Proximal Humerus Fracture Management: A Systematic Review and Meta-Analysis.

This study aims to provide an updated review comparing the complication rates and clinical outcomes of intramedullary nails and locking plates (LPs) in displaced proximal humerus fracture (PHF) management. We performed a systematic review of the Cochrane Central Register of Controlled Trials, Clinical Trials Registry, EMBASE, and PubMed. Studies with level III evidence or higher comparing intramedullary nails and LPs used for internal fixation of displaced PHFs were included. The Methodological Index for Nonrandomized Studies (MINORS) criteria and Cochrane Handbook for Systematic Reviews of Interventions 5.2.0 were used to assess the risk of bias. Our meta-analysis included a comparison of method-related complications, pain scores, range of motion (ROM), and functional scores. A total of 13 comparative studies were included: five randomized controlled trials, three prospective cohort studies, and five retrospective cohort studies. The total number of patients included was 1,253 (677 in the LP group and 576 in the intramedullary nail group). Superior Constant-Murley scores and external rotation ROM were found in the LP group during the early postoperative period. However, long-term functional scores and complication rates were comparable between the two groups. We conclude that intramedullary nailing and LP fixation are both equally effective for the treatment of displaced PHFs. Neither treatment appears superior at this time, and more large-scale randomized controlled trials should be conducted to further evaluate the potential benefit of LPs in the early postoperative period.

Simplified clinical frailty scale design, validation, and adaptation in older patients.

OBJECTIVE: The clinical frailty scale (CFS) evaluates the level of frailty based on clinical examination, comorbidities, and functional and activity levels of older patients. However, there are many difficulties for internists in evaluating frailty with this scale. Therefore, simplifying the CFS with good design and application is required for better treatment outcomes. Our study was conducted to design and evaluate the correlation of a simplified clinical frailty scale (sCFS) with CFS in older patients. PATIENTS AND METHODS: We undertook a cross-sectional analysis involving 279 older patients, which comprised two steps. Step 1 involves the implementation of sCFS, a protocol that has been endorsed by the Geriatrics Professional Council (GPC). Step 2 entails the enrollment of older patients for frailty assessment using sCFS, comparing it with CFS. RESULTS: The study was conducted on 279 older patients; the average age was 75.7 ± 8.4 (years old), and men accounted for 34.8%. There was a high correlation between the sCFS and CFS (Pearson's r = 0.996; p < 0.001). The similarity of the sCFS to the CFS was very high, with Kappa coefficient = 0.984 (p < 0.001). Compared with the CFS, the sCFS had a Youden index of 98% with 100% sensitivity and 98% specificity assessed through the receiver operating characteristic (ROC) with the CFS threshold of 5. CONCLUSIONS: The sCFS can be used to assess frailty with high sensitivity and specificity.

Associations between psychosocial work environment factors and first-time and recurrent treatment for depression: a prospective cohort study of 24,226 employees.

AIMS: Adverse factors in the psychosocial work environment are associated with the onset of depression among those without a personal history of depression. However, the evidence is sparse regarding whether adverse work factors can also play a role in depression recurrence. This study aimed to prospectively examine whether factors in the psychosocial work environment are associated with first-time and recurrent treatment for depression. METHODS: The study included 24,226 participants from the Danish Well-being in Hospital Employees study. We measured ten individual psychosocial work factors and three theoretical constructs (effort-reward imbalance, job strain and workplace social capital). We ascertained treatment for depression through registrations of hospital contacts for depression (International Statistical Classification of Diseases and Related Health Problems version 10 [ICD-10]: F32 and F33) and redeemed prescriptions of antidepressant medication (Anatomical Therapeutic Chemical [ATC]: N06A) in Danish national registries. We estimated the associations between work factors and treatment for depression for up to 2 years after baseline among those without (first-time treatment) and with (recurrent treatment) a personal history of treatment for depression before baseline. We excluded participants registered with treatment within 6 months before baseline. In supplementary analyses, we extended this washout period to up to 2 years. We applied logistic regression analyses with adjustment for confounding. RESULTS: Among 21,156 (87%) participants without a history of treatment for depression, 350 (1.7%) had first-time treatment during follow-up. Among the 3070 (13%) participants with treatment history, 353 (11%) had recurrent treatment during follow-up. Those with a history of depression generally reported a more adverse work environment than those without such a history. Baseline exposure to bullying (odds ratio [OR] = 1.72, 95% confidence interval [95% CI]: 1.30-2.32), and to some extent also low influence on work schedule (OR = 1.27, 95% CI: 0.97-1.66) and job strain (OR = 1.24, 95% CI: 0.97-1.57), was associated with first-time treatment for depression during follow-up. Baseline exposure to bullying (OR = 1.40, 95% CI: 1.04-1.88), lack of collaboration (OR = 1.31, 95% CI: 1.03-1.67) and low job control (OR = 1.27, 95% CI: 1.00-1.62) were associated with recurrent treatment for depression during follow-up. However, most work factors were not associated with treatment for depression. Using a 2-year washout period resulted in similar or stronger associations. CONCLUSIONS: Depression constitutes a substantial morbidity burden in the working-age population. Specific adverse working conditions were associated with first-time and recurrent treatment for depression and improving these may contribute to reducing the onset and recurrence of depression.

Foot-and-mouth disease virus strains isolated in Vietnam during 2010-2019: genetic characterization and antigenic relatedness to the Euro SA vaccine.

Foot-and-mouth disease is a highly contagious disease that affects cloven-hoofed animals. It has an important socio-economic impact on the livestock industry because it produces a drastic decrease of productivity. The disease has been successfully eradicated from some regions, including North America and Western Europe, but it is still endemic in developing countries. Agriculture plays an important role in the national economy of Vietnam, to which animal production contributes a great proportion. The concurrent circulation of foot-and-mouth disease virus (FMDV) serotypes O, A, and Asia 1 has been detected in recent years, but serotype O remains the most prevalent and is responsible for the highest numbers of outbreaks. Appropriate vaccine strain selection is an important element in the control of FMD and is necessary for the application of vaccination programs in FMD-affected regions. Here, we present updated information about the genetic and antigenic characteristics of circulating strains, collected from endemic outbreaks involving types O and A, between 2010 and 2019. Neutralizing assays showed a good in vitro match between type O strains and the monovalent O1 Campos vaccine strain. High r1 values were obtained (above 0.7) when testing a swine serum pool collected 21 days after vaccination, but the O/VTN/2/2019 strain was an exception. An EPP estimation resulted in a median neutralizing titre of about 1.65 log10, indicating that good protection could be achieved. For type A Asia SEA 97 lineage strains, acceptable individual neutralizing titres were obtained with estimated EPP values over 80% for different combinations of vaccine strains. Taking into account that the r1 value is one tool of a battery of tests that should be considered for estimating the cross-protection of a field strain against a vaccine strain, an in vivo challenge experiment was also performed, yielding a PD50 value of 8.0. The results indicate that South American strains could be potentially used for controlling outbreaks involving these lineages. This study demonstrates the importance of considering strain characteristics when choosing vaccine strains and controls.

Phenotyping Down syndrome: discovery and predictive modelling with electronic medical records.

BACKGROUND: Individuals with Down syndrome (DS) have a heightened risk for various co-occurring health conditions, including congenital heart disease (CHD). In this two-part study, electronic medical records (EMRs) were leveraged to examine co-occurring health conditions among individuals with DS (Study 1) and to investigate health conditions linked to surgical intervention among DS cases with CHD (Study 2). METHODS: De-identified EMRs were acquired from Vanderbilt University Medical Center and facilitated creating a cohort of N = 2282 DS cases (55% females), along with comparison groups for each study. In Study 1, DS cases were one-by-two sex and age matched with samples of case-controls and of individuals with other intellectual and developmental difficulties (IDDs). The phenome-disease association study (PheDAS) strategy was employed to reveal co-occurring health conditions in DS versus comparison groups, which were then ranked for how often they are discussed in relation to DS using the PubMed database and Novelty Finding Index. In Study 2, a subset of DS individuals with CHD [N = 1098 (48%)] were identified to create longitudinal data for N = 204 cases with surgical intervention (19%) versus 204 case-controls. Data were included in predictive models and assessed which model-based health conditions, when more prevalent, would increase the likelihood of surgical intervention. RESULTS: In Study 1, relative to case-controls and those with other IDDs, co-occurring health conditions among individuals with DS were confirmed to include heart failure, pulmonary heart disease, atrioventricular block, heart transplant/surgery and primary pulmonary hypertension (circulatory); hypothyroidism (endocrine/metabolic); and speech and language disorder and Alzheimer's disease (neurological/mental). Findings also revealed more versus less prevalent co-occurring health conditions in individuals with DS when comparing with those with other IDDs. Findings with high Novelty Finding Index were abnormal electrocardiogram, non-rheumatic aortic valve disorders and heart failure (circulatory); acid-base balance disorder (endocrine/metabolism); and abnormal blood chemistry (symptoms). In Study 2, the predictive models revealed that among individuals with DS and CHD, presence of health conditions such as congestive heart failure (circulatory), valvular heart disease and cardiac shunt (congenital), and pleural effusion and pulmonary collapse (respiratory) were associated with increased likelihood of surgical intervention. CONCLUSIONS: Research efforts using EMRs and rigorous statistical methods could shed light on the complexity in health profile among individuals with DS and other IDDs and motivate precision-care development.

Strengthening cardiac therapy pipelines using human pluripotent stem cell-derived cardiomyocytes.

Advances in hiPSC isolation and reprogramming and hPSC-CM differentiation have prompted their therapeutic application and utilization for evaluating potential cardiovascular safety liabilities. In this perspective, we showcase key efforts toward the large-scale production of hiPSC-CMs, implementation of hiPSC-CMs in industry settings, and recent clinical applications of this technology. The key observations are a need for traceable gender and ethnically diverse hiPSC lines, approaches to reduce cost of scale-up, accessible clinical trial datasets, and transparent guidelines surrounding the safety and efficacy of hiPSC-based therapies.

Well-differentiated Squamous Cell Carcinoma With Sarcomatous Differentiation in Patient With a History of Recurrent Verrucous Carcinoma.

Human papillomavirus-independent vulvar squamous cell carcinoma has a peak incidence in about the eighth decade of life. A variable portion of the vulvar squamous cell carcinoma are human papillomavirus-independent comprising 20% to 80% of all cases. Verrucous carcinoma (VC) is part of the spectrum of human papillomavirus-independent carcinomas and its combination with well-differentiated squamous cell carcinoma with sarcomatous differentiation is an extremely unusual neoplasm. The available literature on VC is currently limited to case reports and small single-institution studies. Here, we present a case concerning an 81-year-old woman with a history of chronic itching, swelling, and lichen sclerosis with variable-sized multiple white-pink plaques of the vulva. The pathologic diagnosis of VC was made. The patient later on developed multiple lesions of biopsy proved VC and most recent biopsy shows well-differentiated squamous cell carcinoma with abrupt sarcomatous differentiation. A review of the literature shows the rarity of this lesion of the female genital tract. Clinicians and patients should be aware of the aggressive behavior of cancers and adjust their surgical management together with the follow-up strategy. To the best of our knowledge, this is the first description of a VC and well-differentiated squamous cell carcinoma with abrupt sarcomatous differentiation occurring in the vulva.

Spatial Analysis of Drug-Susceptible and Multidrug-Resistant Cases of Tuberculosis, Ho Chi Minh City, Vietnam, 2020-2023.

We characterized the spatial distribution of drug-susceptible (DS) and multidrug-resistant (MDR) tuberculosis (TB) cases in Ho Chi Minh City, Vietnam, a major metropolis in southeastern Asia, and explored demographic and socioeconomic factors associated with local TB burden. Hot spots of DS and MDR TB incidence were observed in the central parts of Ho Chi Minh City, and substantial heterogeneity was observed across wards. Positive spatial autocorrelation was observed for both DS TB and MDR TB. Ward-level TB incidence was associated with HIV prevalence and the male proportion of the population. No ward-level demographic and socioeconomic indicators were associated with MDR TB case count relative to total TB case count. Our findings might inform spatially targeted TB control strategies and provide insights for generating hypotheses about the nature of the relationship between DS and MDR TB in Ho Chi Minh City and the wider southeastern region of Asia.

Sex Differences in Prehospital Identification of Large Vessel Occlusion in Patients With Suspected Stroke.

BACKGROUND: Differences in clinical presentation of acute ischemic stroke between men and women may affect prehospital identification of anterior circulation large vessel occlusion (aLVO). We assessed sex differences in diagnostic performance of 8 prehospital scales to detect aLVO. METHODS: We analyzed pooled individual patient data from 2 prospective cohort studies (LPSS [Leiden Prehospital Stroke Study] and PRESTO [Prehospital Triage of Patients With Suspected Stroke Study]) conducted in the Netherlands between 2018 and 2019, including consecutive patients ≥18 years suspected of acute stroke who presented within 6 hours after symptom onset. Ambulance paramedics assessed clinical items from 8 prehospital aLVO detection scales: Los Angeles Motor Scale, Rapid Arterial Occlusion Evaluation, Cincinnati Stroke Triage Assessment Tool, Cincinnati Prehospital Stroke Scale, Prehospital Acute Stroke Severity, gaze-face-arm-speech-time, Conveniently Grasped Field Assessment Stroke Triage, and Face-Arm-Speech-Time Plus Severe Arm or Leg Motor Deficit. We assessed the diagnostic performance of these scales for identifying aLVO at prespecified cut points for men and women. RESULTS: Of 2358 patients with suspected stroke (median age, 73 years; 47% women), 231 (10%) had aLVO (100/1114 [9%] women and 131/1244 [11%] men). The area under the curve of the scales ranged from 0.70 (95% CI, 0.65-0.75) to 0.77 (95% CI, 0.73-0.82) in women versus 0.69 (95% CI, 0.64-0.73) to 0.75 (95% CI, 0.71-0.79) in men. Positive predictive values ranged from 0.23 (95% CI, 0.20-0.27) to 0.29 (95% CI, 0.26-0.31) in women versus 0.29 (95% CI, 0.24-0.33) to 0.37 (95% CI, 0.32-0.43) in men. Negative predictive values were similar (0.95 [95% CI, 0.94-0.96] to 0.98 [95% CI, 0.97-0.98] in women versus 0.94 [95% CI, 0.93-0.95] to 0.96 [95% CI, 0.94-0.97] in men). Sensitivity of the scales was slightly higher in women than in men (0.53 [95% CI, 0.43-0.63] to 0.76 [95% CI, 0.68-0.84] versus 0.49 [95% CI, 0.40-0.57] to 0.63 [95% CI, 0.55-0.73]), whereas specificity was lower (0.79 [95% CI, 0.76-0.81] to 0.87 [95% CI, 0.84-0.89] versus 0.82 [95% CI, 0.79-0.84] to 0.90 [95% CI, 0.88-0.91]). Rapid arterial occlusion evaluation showed the highest positive predictive values in both sexes (0.29 in women and 0.37 in men), reflecting the different event rates. CONCLUSIONS: aLVO scales show similar diagnostic performance in both sexes. The rapid arterial occlusion evaluation scale may help optimize prehospital transport decision-making in men as well as in women with suspected stroke.

Genetic diversity of G9, G3, G8 and G1 rotavirus group A strains circulating among children with acute gastroenteritis in Vietnam from 2016 to 2021.

Rotavirus group A (RVA) is the most common cause of severe childhood diarrhea worldwide. The introduction of rotavirus vaccination programs has contributed to a reduction in hospitalizations and mortality caused by RVA. From 2016 to 2021, we conducted surveillance to monitor RVA prevalence and genotype distribution in Nam Dinh and Thua Thien Hue (TT Hue) provinces where a pilot Rotavin-M1 vaccine (Vietnam) implementation took place from 2017 to 2020. Out of 6626 stool samples, RVA was detected in 2164 (32.6%) by ELISA. RT-PCR using type-specific primers were used to determine the G and P genotypes of RVA-positive specimens. Whole genome sequences of a subset of 52 specimens randomly selected from 2016 to 2021 were mapped using next-generation sequencing. From 2016 to 2021, the G9, G3 and G8 strains dominated, with detected frequencies of 39%, 23%, and 19%, respectively; of which, the most common genotypes identified were G9P[8], G3P[8] and G8P[8]. G1 strains re-emerged in Nam Dinh and TT Hue (29.5% and 11.9%, respectively) from 2020 to 2021. G3 prevalence decreased from 74% to 20% in TT Hue and from 21% to 13% in Nam Dinh province between 2017 and 2021. The G3 strains consisted of 52% human typical G3 (hG3) and 47% equine-like G3 (eG3). Full genome analysis showed substantial diversity among the circulating G3 strains with different backgrounds relating to equine and feline viruses. G9 prevalence decreased sharply from 2016 to 2021 in both provinces. G8 strains peaked during 2019-2020 in Nam Dinh and TT Hue provinces (68% and 46%, respectively). Most G8 and G9 strains had no genetic differences over the surveillance period with very high nucleotide similarities of 99.2-99.9% and 99.1-99.7%, respectively. The G1 strains were not derived from the RVA vaccine. Changes in the genotype distribution and substantial diversity among circulating strains were detected throughout the surveillance period and differed between the two provinces. Determining vaccine effectiveness against circulating strains over time will be important to ensure that observed changes are due to natural secular variation and not from vaccine pressure.

Synthesis of 2-benzyl benzoxazoles and benzothiazoles via elemental sulfur promoted cyclization of styrenes with 2-nitrophenols and N,N-dialkyl-3-nitroanilines.

Herein we report a method for affording 2-benzyl benzoxazoles from substituted styrenes and 2-nitrophenols. The success of this method relies on the use of simple reagents, namely elemental sulfur and DABCO. A combination of identical reagents was utilized for the annulation of styrenes with N,N-dialkyl-3-nitroanilines to afford 2-benzyl benzothiazoles. Overall, benzoxazoles and benzothiazoles bearing useful functionalities such as halogens, amines, and heterocyclic groups were isolated in moderate to good yields. Our methods are a rare example of divergent transformations of substituted nitroarenes towards 2-benzyl benzoxazoles and benzothiazoles.

Perlecan (HSPG2) promotes structural, contractile, and metabolic development of human cardiomyocytes.

Perlecan (HSPG2), a heparan sulfate proteoglycan similar to agrin, is key for extracellular matrix (ECM) maturation and stabilization. Although crucial for cardiac development, its role remains elusive. We show that perlecan expression increases as cardiomyocytes mature in vivo and during human pluripotent stem cell differentiation to cardiomyocytes (hPSC-CMs). Perlecan-haploinsuffient hPSCs (HSPG2+/-) differentiate efficiently, but late-stage CMs have structural, contractile, metabolic, and ECM gene dysregulation. In keeping with this, late-stage HSPG2+/- hPSC-CMs have immature features, including reduced ⍺-actinin expression and increased glycolytic metabolism and proliferation. Moreover, perlecan-haploinsuffient engineered heart tissues have reduced tissue thickness and force generation. Conversely, hPSC-CMs grown on a perlecan-peptide substrate are enlarged and display increased nucleation, typical of hypertrophic growth. Together, perlecan appears to play the opposite role of agrin, promoting cellular maturation rather than hyperplasia and proliferation. Perlecan signaling is likely mediated via its binding to the dystroglycan complex. Targeting perlecan-dependent signaling may help reverse the phenotypic switch common to heart failure.

Clinical and technical factors in endoscopic skull base surgery associated with reconstructive success.

BACKGROUND: In this study, we identified key discrete clinical and technical factors that may correlate with primary reconstructive success in endoscopic skull base surgery (ESBS). METHODS: ESBS cases with intraoperative cerebrospinal fluid (CSF) leaks at four tertiary academic rhinology programs were retrospectively reviewed. Logistic regression identified factors associated with surgical outcomes by defect subsite (anterior cranial fossa [ACF], suprasellar [SS], purely sellar, posterior cranial fossa [PCF]). RESULTS: Of 706 patients (50.4% female), 61.9% had pituitary adenomas, 73.4% had sellar or SS defects, and 20.5% had high-flow intraoperative CSF leaks. The postoperative CSF leak rate was 7.8%. Larger defect size predicted ACF postoperative leaks; use of rigid reconstruction and older age protected against sellar postoperative leaks; and use of dural sealants compared to fibrin glue protected against PCF postoperative leaks. SS postoperative leaks occurred less frequently with the use of dural onlay. Body-mass index, intraoperative CSF leak flow rate, and the use of lumbar drain were not significantly associated with postoperative CSF leak. Meningitis was associated with larger tumors in ACF defects, nondissolvable nasal packing in SS defects, and high-flow intraoperative leaks in PCF defects. Sinus infections were more common in sellar defects with synthetic grafts and nondissolvable nasal packing. CONCLUSIONS: Depending on defect subsite, reconstructive success following ESBS may be influenced by factors, such as age, defect size, and the use of rigid reconstruction, dural onlay, and tissue sealants.

A disposable immunosensor for the detection of salivary MMP-8 as biomarker of periodontitis.

This work describes the development of a novel voltammetric immunosensor for the detection of salivary MMP-8 at the point-of-care. The electrochemical platform was based on a graphene (GPH) screen-printed electrode (SPE) functionalized by gold-nanospheres (AuNSs) and antibodies against MMP-8 protein (anti-MMP-8). The functionalization with anti-MMP-8 was realized by using 11-mercaptoundecanoic acid (11-MUA), thanks to its ability to give strong sulfur bonds with its -SH end, and to cross-link the -NH2 groups of the antibody molecule with the other -COOH end, using the traditional EDC-NHS method. The voltammetric sensor showed good performances with a linear range of 2.5-300 ng mL-1, a LOD value of 1.0 ± 0.1 ng mL-1 and a sensitivity of 0.05 µA mL cm-2 ng-1. Moreover, the proposed immunosensor was tested in real saliva samples, showing comparable results to those obtained with the conventional ELISA method. The biosensor was single-use and cost-effective and required a small quantity of test medium and a short preparation time, representing a very attractive biosensor for MMP-8 detection in human saliva.