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Meningocele, a rare subtype of cephalocele, can manifest in various positions and exhibit diverse characteristics. On the other hand, dacryocystocele, also a rare anatomical disorder, typically presents as a cyst located between the nose and the eye. Generally, distinguishing between these 2 lesions is not difficult. The presented case involves a fetus with suspected dacryocystocele, ultimately diagnosed postpartum as meningocele, underscoring the complexities in distinguishing between these conditions. The article details the patient’s prenatal examinations, imaging findings, and the subsequent surgical intervention, highlighting the significance of meticulous diagnosis for effective prenatal management. The case illuminates the potential oversight and misdiagnosis challenges associated with atypical cephaloceles, contributing valuable insights for clinicians involved in prenatal diagnosis and management.

Background The standard treatment for localized osteosarcoma is neoadjuvant chemotherapy before surgery, followed by adjuvant chemotherapy. Our aim was to report the rate of histopathological response to neoadjuvant chemotherapy for the treatment of extremity osteosarcoma in Vietnam. Methods We performed a retrospective study of stage II conventional osteosarcoma patients under 40 years-old who received MAP regimen as neoadjuvant chemotherapy at the Vietnam National Cancer Hospital between June 2019 and June 2022. Histopathological response was evaluated using the Huvos grading system, in which a good histopathological response was defined as a necrotic rate of 90% or more. Results Thirty-five eligible patients were included in the study. Male patients accounted for 65.7%, with a median age of 16 years (range, 8-38 years). Of the 35 cases, 31 were reported as stage IIB (88.6%). The femur and tibia were the most common sites in our study, accounting for 51.4% and 34.3%, respectively. The most common pathologic subtype was osteoblastic osteosarcoma (68.6%), followed by chondroblastic subtype (20%). After two cycles of MAP-regimen neoadjuvant chemotherapy, 28 of 35 patients (80%) underwent limb-sparing surgery. A good histopathological response was observed in 18 of 35 patients (51.4%). There were significant correlations between the duration of symptoms ( P = 0.016), LDH ( P = 0.001) serum levels at initial presentation, and ALP ( P = 0.043) serum levels at initial presentation with histopathological response. Conclusion This retrospective study suggests a possible association between symptom duration, pre-treatment LDH levels, and pre-treatment ALP levels with histopathological response rates. Additional clinical investigations with long-term follow-up are needed to investigate survival outcomes in the Asian population.

Acute methanol intoxication is uncommon. Methanol is mildly toxic, but its metabolites are formic acid and formaldehyde, causing total metabolism, visual disturbances, and central nervous system disturbances, leading to coma and death. Magnetic resonance imaging (MRI) is very important for the diagnosis and prognosis of methanol intoxication. Putaminal necrosis with or without hemorrhage is the most frequently reported finding. Other affected areas that are reported in the literature are subcortical white matter, hippocampus, optic nerve, and cerebellum. We report 3 cases of methanol intoxication and discuss their brain lesions on MRI.

Subcutaneous panniculitis-like T-cell lymphoma (SPTLP), a unique variant of primary cutaneous T-cell lymphomas, clinically mimics subcutaneous panniculitis. It is typified by the development of multiple plaques or subcutaneous erythematous nodules, predominantly on the extremities and trunk. Epidemiological findings reveal a greater incidence in females than males, affecting a wide demographic, including pediatric and adult cohorts, with a median onset age of around 30 years. Diagnosis of SPTLP is complex, hinging on skin biopsy analyses and the identification of T-cell lineage-specific immunohistochemical markers. Treatment modalities for SPTLP are varied; while corticosteroids may be beneficial initially for many patients, a substantial number require chemotherapy, especially in cases of poor response or relapse. Generally, SPTLP progresses slowly, yet approximately 20% of cases advance to hemophagocytic lymphohistiocytosis (HLH), often correlating with a negative prognosis. We report a case of a young male patient presenting with prolonged fever, multiple skin lesions accompanied by HLH, a poor clinical course, and eventual death, diagnosed postmortem with SPTLP. In addition, we also present a literature review of the current evidence of some updates related to SPTLP.

Chyle leak is a rare and serious condition caused by damaged lymphatic vessels. It can occur after retroperitoneal surgery involving extensive lymphadenectomy for kidney cancer. Besides lymphatic channel damage, the obstruction of the thoracic duct worsens the leakage. Managing patients with thoracic duct obstruction and postsurgical chyle leakage is challenging due to limited data on how to handle this condition. In this case report, a 28-year-old female patient underwent left nephrectomy for left kidney cancer. Three days after the surgery, milky fluid drained from the left renal fossa. Conservative treatment failed, and further examination through magnetic resonance lymphangiography revealed the absence of the thoracic duct and contrast extravasation at the left renal fossa. Lymphangiography confirmed distal thoracic duct obstruction. The patient's condition was successfully managed by using thoracic duct stenting.This report contributes to the understanding that thoracic duct obstruction can lead to lymphatic collateral circulation within the abdomen, thereby increasing the risk of postoperative chylous leak.

Isolated major aortopulmonary collateral artery (MAPCA), in the absence of evidence of structural heart disease, is a very rare observation. This anomaly usually appears in preterm newborns. In the majority of babies, isolated MAPCAs cause no symptoms and regress spontaneously after birth and their conservative management is usually sufficient. We report a case of an asymptomatic full-term 5-month-old infant presenting with heart murmur as the only sign during clinical evaluation. Echocardiography revealed a dilated left ventricle, with no pulmonary hypertension. Computed tomography angiogram showed a large MAPCA arising from the descending thoracic aorta and supplying blood to the left lower lobe. The condition was managed successfully by percutaneous obliteration with Amplatzer vascular plugs. Isolated MAPCA is usually a benign anomaly, presenting no clinical finding and requiring no specific treatment. However, in a small minority of infants, this congenital disorder may progress, with detrimental impacts on cardiac structure before clinical symptoms appear. Early intervention may be required to prevent irreversible sequelae.

Pericardial agenesis is a rare congenital defect that is generally asymptomatic. We describe a case of pericardial agenesis that was incidentally discovered through the development of hemorrhagic pleural effusion as a complication during percutaneous coronary intervention. (Level of Difficulty: Advanced.)

Umbilical artery calcification is a rare finding with only a small number of cases reported on radiographs. To date, no cases have been described on ultrasound. Reported cases were limited to the horizontal segment of the medial umbilical ligament. This case report presents a unique case of ultrasound findings of bilateral umbilical artery calcification within the vertical (distal) segment of the medial umbilical ligament.

Renal trauma occurring in patients with unilateral renal cystic disease (URCD) is extremely rare. Unilateral renal cystic disease is benign, nonprogressive, nonfamilial, nonencapsulated, and unrelated to cysts in other organs. It should be differentiated from autosomal dominant polycystic kidney disease (ADPKD) parenthesis, multicystic dysplastic kidney disease, multiple renal simple cysts, and cystic renal neoplasms. We report a case of a 15-year-old male with URCD admitted to the hospital sustaining blunt trauma to his right flank after a motor vehicle crash. Final diagnosis in this case was renal injury in a URCD patient. The patient was treated conservatively and subsequently discharged. Unilateral renal cystic disease can be diagnosed and followed by a combination of imaging methods and functional studies. The management of URCD is conservative. Although the disease is stable, nephrectomy may occasionally be indicated when there is a strong suspicion for malignancy.

Objective This review aimed to systematically determine the optimal nasal saline regimen for different types of sinonasal diseases. Data Sources PubMed, Embase, SCOPUS, Cochrane Library, Web of Science, ClinicalTrials.gov. The last search was on December 6, 2021. Review Methods Study selection was done by 2 independent authors. Randomized controlled trials and meta-analyses were included. The effects of nasal saline treatment through various devices, saline tonicities, and buffer statuses were evaluated in patients with allergic and nonallergic rhinitis, acute and chronic rhinosinusitis (CRS), CRS with cystic fibrosis, and postoperative care, including septoplasty/turbinoplasty and endoscopic sinus surgery. Results Sixty-nine studies were included: 10 meta-analyses and 59 randomized controlled trials. For allergic rhinitis, large-volume devices (≥60 mL) were effective for treating adults, while low-volume devices (5-59 mL) were effective for children. Isotonic saline was preferred over hypertonic saline due to fewer adverse events. For acute rhinosinusitis, saline irrigation was beneficial in children, but it was an option for adults. Large-volume devices were more effective, especially in the common cold subgroup. For CRS, large-volume devices were effective for adults, but saline drop was the only regimen that had available data in children. Buffered isotonic saline was more tolerable than nonbuffered or hypertonic saline. The data for CRS with cystic fibrosis and nonallergic rhinitis were limited. For postoperative care, buffered isotonic saline delivered by large-volume devices was effective. Conclusion Nasal saline treatment is recommended for treating most sinonasal diseases. Optimal delivery methods for each condition should be considered to achieve therapeutic effects of saline treatment.

ABSTRACT: Introduction: Several studies have reported women's worry that sexual intercourse may harm the course of pregnancy. This worry might lead to avoidance of sexual intercourse during pregnancy. Aim: To assess if fears about harming the pregnancy are associated with avoidance of sexual intercourse during pregnancy. Methods: A cross-sectional study was conducted on 250 Vietnamese pregnant women in the first or second trimester who visited our hospital for antenatal care. We explored 5 types of fears including miscarriage/preterm labor, premature rupture of membranes, bleeding, infection, and injury to the fetus. Fears were measured by modified questions from the Reasons For Not Engaging in Sexual Activity During Pregnancy questionnaire. Using the total fear score, pregnant women were categorized into having low, moderate, and high fear. Main Outcome Measure: Not having sexual intercourse during the past 4 weeks. Results: 72 (28.8%) pregnant women had no sexual intercourse for the past 4 weeks. All types of fear were considered important among pregnant women; the more important fears were infection and injury to the fetus. In multivariable regression analysis, the prevalence of not having sexual intercourse was higher in both women who had moderate (adjusted prevalence ratio = 2.84, 95% CI 1.42–5.67) and high fear (adjusted prevalence ratio = 4.39, 95% CI 2.28–8.44). Conclusion: Avoidance of sexual intercourse was common among Vietnamese pregnant women and was associated with the fears about harming the pregnancy. This can be a target in the health education programs for pregnancy couples.Thanh C. Phan, Long B. Hoang, Thanh K. Tran, et al. Fear-Related Reasons for Avoiding Sexual Intercourse in Early Pregnancy: A Cross-Sectional Study. Sex Med 2021;9:100430.

Controversy persists regarding the safety and efficacy of an accelerated low-dose recombinant tissue-type plasminogen activator (rt-PA) regimen for reperfusion therapy in acute pulmonary embolism. This study describes the outcomes of an accelerated low-dose rt-PA regimen for the treatment of acute pulmonary embolism in Vietnamese patients. This was a case series from October 2014 to October 2020 from 9 hospitals across Vietnam. Patients presenting with acute pulmonary embolism with high to intermediate mortality risk were administered alteplase 0.6 mg per kilogram (maximum of 50 mg) over 15 min. The main outcomes were the proportion who survived to hospital discharge and at 3 months as well as in-hospital hemorrhage (major and minor according to International Society of Thrombosis and Hemhorrage definitions). A total of 80 patients were enrolled: 48 (60%) with high risk for mortality and 32 patients (40%) with intermediate risk for mortality. A total of 7 (8.8%) died in hospital. All deaths occurred in the high-risk mortality group. The 73 patients who were discharged alive remained alive at 3 months follow up. During hospitalization, 1 patient (1.3%) suffered major bleeding, and 7 (8.8%) had minor bleeding. An accelerated thrombolytic regimen with alteplase 0.6 mg/kg (maximum of 50 mg) over 15 min for acute pulmonary embolism appeared be effective and safe in a case series of Vietnamese patients.

Introduction: Although communal smoking of hookah by means of water pipes is perceived to be a safe alternative to cigarette smoking, the effects of hookah smoke in respiratory epithelia have not been well characterized. This study evaluated epigenomic and transcriptomic effects of hookah smoke relative to cigarette smoke in human respiratory epithelial cells. Methods: Primary normal human small airway epithelial cells from three donors and cdk4 and hTERT-immortalized small airway epithelial cells and human bronchial epithelial cells were cultured for 5 days in normal media with or without cigarette smoke condensates (CSCs) or water pipe condensates (WPCs). Cell count, immunoblot, RNA sequencing, quantitative real-time reverse-transcriptase polymerase chain reaction, methylation-specific polymerase chain reaction, and quantitative chromatin immunoprecipitation techniques were used to compare effects of hookah and cigarette smoke on cell proliferation, global histone marks, gene expression, and promoter-related chromatin structure. Results: CSC and WPC decreased global H4K16ac and H4K20me3 histone marks and mediated distinct and overlapping cancer-associated transcriptome signatures and pathway modulations that were cell line dependent and stratified across lung cancer cells in a histology-specific manner. Epiregulin encoding a master regulator of EGFR signaling that is overexpressed in lung cancers was up-regulated, whereas FILIP1L and ABI3BP encoding mediators of senescence that are repressed in lung cancers were down-regulated by CSC and WPC. Induction of epiregulin and repression of FILIP1L and ABI3BP by these condensates coincided with unique epigenetic alterations within the respective promoters. Conclusions: These findings support translational studies to ascertain if hookah-mediated epigenomic and transcriptomic alterations in cultured respiratory epithelia are detectable and clinically relevant in hookah smokers.

Metacarpal fractures are common upper-extremity fractures. Surgical fixation is recommended for open injuries, segmental bone loss, multiple metacarpal fractures, irreducible fractures, and unstable fracture patterns. For transverse and short oblique metacarpal shaft fracture patterns, intramedullary headless compression screws have been added most recently as a surgical option. Intramedullary headless compression screw fixation has been performed in a retrograde manner in which a guidewire and then a cannulated headless screw are placed through a skin excision, a split in the sagittal band or extensor tendon, and the dorsal central articular cartilage surface of the metacarpal head. Here, we describe a step-by-step novel approach to fixation of transverse and short oblique proximal and midshaft metacarpal fractures through an antegrade approach using intramedullary headless compression screws with a detailed 4K high-definition video demonstration and 2 clinical cases involving the middle and ring metacarpals. This surgical alternative addresses many concerns with the retrograde technique and avoids creating defects in the extensor tendon, the sagittal hood, the articular surface of the metacarpal head at the metacarpophalangeal joint, and the articulating surface of the trapezium, capitate, and hamate at the carpometacarpal articulation. Key words: antegrade intramedullary screw, metacarpal fracture fixation, midshaft, minimally invasive, proximal third

Summary: Background: By 2050, almost 5 billion people globally are projected to have myopia, of whom 20% are likely to have high myopia with clinically significant risk of sight-threatening complications such as myopic macular degeneration. These are diagnoses that typically require specialist assessment or measurement with multiple unconnected pieces of equipment. Artificial intelligence (AI) approaches might be effective for risk stratification and to identify individuals at highest risk of visual loss. However, unresolved challenges for AI medical studies remain, including paucity of transparency, auditability, and traceability. Methods: In this retrospective multicohort study, we developed and tested retinal photograph-based deep learning algorithms for detection of myopic macular degeneration and high myopia, using a total of 226 686 retinal images. First we trained and internally validated the algorithms on datasets from Singapore, and then externally tested them on datasets from China, Taiwan, India, Russia, and the UK. We also compared the performance of the deep learning algorithms against six human experts in the grading of a randomly selected dataset of 400 images from the external datasets. As proof of concept, we used a blockchain-based AI platform to demonstrate the real-world application of secure data transfer, model transfer, and model testing across three sites in Singapore and China. Findings: The deep learning algorithms showed robust diagnostic performance with areas under the receiver operating characteristic curves [AUC] of 0·969 (95% CI 0·959–0·977) or higher for myopic macular degeneration and 0·913 (0·906–0·920) or higher for high myopia across the external testing datasets with available data. In the randomly selected dataset, the deep learning algorithms outperformed all six expert graders in detection of each condition (AUC of 0·978 [0·957–0·994] for myopic macular degeneration and 0·973 [0·941–0·995] for high myopia). We also successfully used blockchain technology for data transfer, model transfer, and model testing between sites and across two countries. Interpretation: Deep learning algorithms can be effective tools for risk stratification and screening of myopic macular degeneration and high myopia among the large global population with myopia. The blockchain platform developed here could potentially serve as a trusted platform for performance testing of future AI models in medicine. Funding: None.

The 2019 novel coronavirus (COVID-19) pandemic has prompted the reorganization in the scheduling and method of care for many patients, including patients diagnosed with cancer. Cancer patients, who have an immunocompromised status, may be at a higher risk of severe symptoms from infection with COVID-19. While information is rapidly evolving regarding COVID-19, Canada, both nationally and provincially, has been conveying new information to patients online. We assessed the content and readability of COVID-19-related online Canadian patient education material (PEM) for cancer patients to determine if the content of the material was written at a grade reading level that the majority of Canadians can understand. PEMs were extracted from provincial cancer agencies and the national Canadian Cancer Society, evaluated using 10 readability scales, qualitatively analyzed to identify their themes and difficult word content. Thirty-eight PEMs from both national and provincial cancers associations were, on average, written above the recommended 7th grade level. Each of the associations ’ average grade levels were: BC Cancer (11.00 95% confidence interval [CI] 8.27-13.38), CancerControl Alberta (10.46 95% CI 8.29-12.62), Saskatchewan Cancer Agency (11.08 95% CI 9.37-12.80), Cancer Care Manitoba (9.55 95% CI 6.02-13.01), Cancer Care Ontario (9.35 95% CI 6.80-11.90), Cancer Care Nova Scotia (10.95 95% CI 9.86-12.04), Cancer Care Eastern Health Newfoundland and Labrador (10.14 95% CI 6.87-13.41), and the Canadian Cancer Society (10.06 95% CI 8.07-12.05). Thematic analysis identified 4 themes: public health strategy, information about COVID-19, patient instructions during COVID-19, and resources. Fifty-three percent of the complex words identified were medical jargon. This represents an opportunity to improve PEM readability, to allow for greater comprehension amongst a wider target audience.

Renal arteriovenous fistulas are rare complications of kidney injury that are usually caused by penetrating or blunt abdominal trauma, percutaneous or open biopsy, or surgery. We report a case of renal arteriovenous fistula after blunt abdominal trauma of a male patient who had traffic accidents. Computed tomography images show arteriovenous fistula lesion mimicking the tumor of the renal pelvis. Through this case, we present how to identify and avoid being confused in diagnosis as well as introduce its clinical manifestations, imaging, and treatment.

Background:. Recurrence rates following surgical intervention for Dupuytren's disease (DD) remains high. In this study, we investigate the use of acellular dermal matrix (ADM) to reduce recurrence and improve long-term clinical outcome. Methods:. We examined 132 patients undergoing open fasciectomy for DD from 2007 to 2017. The experimental group had a sheet of ADM (FlexHD) sutured into the surgical bed controls were not closed with ADM. Patient characteristics, range of motion, and complications were examined. Results:. Twenty-eight (21.2%) patients were treated with acellular dermal matrix, whereas 104 (78.8%) patients were not. The median age was 67.0 years (range 34–91 years). with no differences between group regarding age, comorbidities, and laterality. The mean preoperative interphalangeal joint flexion contracture in the ADM group of 66.5 ± 29.9 degrees was corrected to 9.7 ± 12.4 degrees, whereas the mean metacarpophalangeal joint preoperative flexion contracture of 51.4 ± 23.9 degrees was corrected to 7.8 ± 14.1 degrees at postoperative examination (P < 0.05). The median follow-up was 18.7 months, during which the recurrence of contracture was observed in 1 of 28 patients in the group receiving ADM compared with 9 of 104 in the control group (P = 0.37). There were no differences in the incidence of minor wound complications observed. Conclusion:. The adjunct placement of acellular dermal matrix into the wound bed following fasciectomy for DD may be an important surgical strategy to reduce recurrence rates as well as augment coverage of exposed vital structures in cases of severe flexion contracture.

Background:. Plastic surgery residency program websites (PSRWs) remain a major resource for applicants to one of the most competitive specialties in medicine, yet it is unclear how the website content aligns with information applicants need. Objective:. To evaluate PSRWs and whether they are meeting applicant needs. Methods:. An anonymous online survey of 2016 plastic and reconstructive surgery applicants evaluated the use of PSRWs and information desired. Two researchers then independently analyzed all 93 PSRWs in the United States to determine whether the websites met the needs of applicants based on a quantitative scoring system. Results:. Out of 369 total applicants to plastic surgery, the survey was sent to the 189 applicants to University of Southern California, and 87 responded (46% response rate). Ninety-eight percentage of respondents used websites during the application process. For 31%, websites served as the only source of information. Websites were moderately (60%) and only slightly useful (32%). For 22% and 34%, the quality of a website influenced their decision to apply or interview, respectively. Out of the 22 common components between the applicant survey and scoring assessment of websites, there was a significant difference in 17 components (77%) between those rated as “important” by applicants and availability of the corresponding component on websites (P < 0.05). Average (SD) score among websites was 18.7 (5.3) out of 49 maximum points (36.9%). Over 30% of websites displayed broken links or missing or outdated information. Only 19.6% displayed a link to provide website feedback. Conclusions:. PSRWs commonly include pertinent information that is useful; however, most are lacking components valued by applicants. These findings can help guide the design, content, and improvement of PSRWs to be quality resources for applicants.

Background: Inappropriate antibiotic use for acute respiratory tract infections is common in primary health care, but distinguishing serious from self-limiting infections is difficult, particularly in low-resource settings. We assessed whether C-reactive protein point-of-care testing can safely reduce antibiotic use in patients with non-severe acute respiratory tract infections in Vietnam. Method: We did a multicentre open-label randomised controlled trial in ten primary health-care centres in northern Vietnam. Patients aged 1–65 years with at least one focal and one systemic symptom of acute respiratory tract infection were assigned 1:1 to receive either C-reactive protein point-of-care testing or routine care, following which antibiotic prescribing decisions were made. Patients with severe acute respiratory tract infection were excluded. Enrolled patients were reassessed on day 3, 4, or 5, and on day 14 a structured telephone interview was done blind to the intervention. Randomised assignments were concealed from prescribers and patients but not masked as the test result was used to assist treatment decisions. The primary outcome was antibiotic use within 14 days of follow-up. All analyses were prespecified in the protocol and the statistical analysis plan. All analyses were done on the intention-to-treat population and the analysis of the primary endpoint was repeated in the per-protocol population. This trial is registered under number NCT01918579. Findings: Between March 17, 2014, and July 3, 2015, 2037 patients (1028 children and 1009 adults) were enrolled and randomised. One adult patient withdrew immediately after randomisation. 1017 patients were assigned to receive C-reactive protein point-of-care testing, and 1019 patients were assigned to receive routine care. 115 patients in the C-reactive protein point-of-care group and 72 patients in the routine care group were excluded in the intention-to-treat analysis due to missing primary endpoint. The number of patients who used antibiotics within 14 days was 581 (64%) of 902 patients in the C-reactive protein group versus 738 (78%) of 947 patients in the control group (odds ratio [OR] 0·49, 95% CI 0·40–0·61; p

Supernumerary teeth are those that form in excess to the normal dental formula and while there is no clear pathogenesis for their formation, they are known to vary in size, morphology, location and presentation. We present two cases of otherwise healthy patients who presented with pain, discomfort and discharge from the nasal passages. CT imaging identified a tooth-like density present in the bone of the nasal floor in both patients. In both cases, the tooth was extracted surgically under anaesthetic. A symptomatic supernumerary in the nasal floor might cause a plethora of symptoms and complications, decreasing the overall quality of life for a patient. Patients who present with a supernumerary tooth in the nasal floor should be further investigated with a simple nasal speculum examination and a CT scan. Their surgical management is simple and brings near immediate relief of symptoms. [ABSTRACT FROM AUTHOR]

This article describes the synthesis of a difluorinated CinNapht derivative in the 4' and 5' positions allowing the easy access to two new families of fluorophores by late-stage functionalization using SNAr. The first one comprises derivatives incorporating hindered aromatic amines in the 4' and 5' positions, which show redemission in apolar solvents. The second one is obtained through the use of dinucleophiles. Among them, Tetrahydroquinoxaline (THQ) and tetrahydrobenzodiazepine (THB) compounds show strongly redshifted emission. The photophysical properties of all the fluorophores in these two families are studied and rationalized by DFT and TDDFT calculations. The most promising compounds have been used to image living cells by confocal microscopy., (© 2024 Wiley‐VCH GmbH.)

Lifestyle, diet, socioeconomic status and genetics all contribute to heterogeneity in immune responses. Vietnam is plagued with a variety of health problems, but there are no available data on immune system values in the Vietnamese population. This study aimed to establish reference intervals for immune cell parameters specific to the healthy Vietnamese population by utilizing multi-color flow cytometry (MCFC). We provide a comprehensive analysis of total leukocyte count, quantitative and qualitative shifts within lymphocyte subsets, serum and cytokine and chemokine levels and functional attributes of key immune cells including B cells, T cells, natural killer (NK) cells and their respective subpopulations. By establishing these reference values for the Vietnamese population, these data contribute significantly to our understanding of the human immune system variations across diverse populations. These data will be of substantial comparative value and be instrumental in developing personalized medical approaches and optimizing diagnostic strategies for individuals based on their unique immune profiles., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 VinUniversity.)

This article describes the synthesis and photophysical properties of Aggregation-Induced Emission (enhancement) luminogens derivated from CinNaphts dyes. These fluorophores can be obtained in good yields in a single SNAr step of a fluorinated CinNapht derivative by incorporating hindered aromatic amines. They exhibit AIE(E) behavior associated with solid-state fluorescence covering an emission range from 563 to 722 nm. One carbazole derivative demonstrates a remarkable efficiency in imaging lipid droplets in living cells through an original photophysical mechanism.

Background: The omnipresence of population heterogeneity in industrial bioprocesses originates from prevailing dynamic bioprocess conditions, which promote differences in the expression of cellular characteristics. Despite the awareness, the concrete consequences of this phenomenon remain poorly understood., Results: Therefore, for the first time, a L-phenylalanine overproducing Escherichia coli quadruple reporter strain was established for monitoring of general stress response, growth behavior, oxygen limitation and product formation of single cells based on mTagBFP2, mEmerald, CyOFP1, and mCardinal2 expression measured by flow cytometry. This strain was applied for the fed-batch production of L-phenylalanine from glycerol and ammonia in a stirred-tank bioreactor at homogeneous conditions compared to the same process in a novel two-compartment bioreactor. This two-compartment bioreactor consists of a stirred-tank bioreactor with an initial volume of 0.9 L (homogeneous zone) with a coiled flow inverter with a fixed working volume of 0.45 L as a bypass (limitation zone) operated at a mean hydraulic residence time of 102 s. The product formation was similar in both bioreactor setups with maximum L-phenylalanine concentrations of 21.1 ± 0.6 g L -1 demonstrating the consistency of this study's microbial L-phenylalanine production. However, cell growth was vulnerable to repetitive exposure to the dynamically changing conditions in the two-compartment bioreactor with maximum biomass yields reduced by 21%. The functionality of reporter molecules was approved in the stirred-tank bioreactor cultivation, in which expressed fluorescence levels of all four markers were in accordance with respective process state variables. Additional evaluation of the distributions on single-cell level revealed the presence of population heterogeneity in both bioprocesses. Especially for the marker of the general stress response and the product formation, the corresponding histograms were characterized by bimodal shapes and broad distributions. These phenomena were pronounced particularly at the beginning and the end of the fed-batch process., Conclusions: The here shown findings confirm multiple reporter strains to be a noninvasive tool for monitoring cellular characteristics and identifying potential subpopulations in bioprocesses. In combination with experiments in scale-down setups, these can be utilized for a better physiological understanding of bioprocesses and support future scale-up procedures., (© 2023. BioMed Central Ltd., part of Springer Nature.)

When targeting robust, high-yielding bioprocesses, phenomena such as population heterogeneity have to be considered. Therefore, the influence of the conditions which the cells experience prior to the main culture should also be evaluated. Here, the influence of a pre-culture medium (complex vs. minimal medium), optical density for inoculation of the main culture (0.005, 0.02 and 0.0125) and harvest time points of the pre-culture in exponential growth phase (early, mid and late) on the level of population heterogeneity in batch cultures of the Escherichia coli triple reporter strain G7 BL21(DE3) in stirred-tank bioreactors was studied. This strain allows monitoring the growth ( rrnB -EmGFP), general stress response ( rpoS -mStrawberry) and oxygen limitation ( nar -TagRFP657) of single cells through the expression of fluorescent proteins. Data from batch cultivations with varying pre-culture conditions were analysed with principal component analysis. According to fluorescence data, the pre-culture medium had the largest impact on population heterogeneities during the bioprocess. While a minimal medium as a pre-culture medium elevated the differences in cellular growth behaviour in the subsequent batch process, a complex medium increased the general stress response and led to a higher population heterogeneity. The latter was promoted by an early harvest of the cells with low inoculation density. Seemingly, nar -operon expression acted independently of the pre-culture conditions.

A simple and easy-to-implement process based on a nucleophilic aromatic substitution reaction with a wide variety of nucleophiles on a fluorinated CinNapht is described. This process has the key advantage of introducing multiple functionalities at a very late stage, thus providing access to new applications including the synthesis of photostable and bioconjugatable large Stokes shift red emitting dyes and selective organelle imaging agents, as well as AIEE-based wash-free lipid droplet imaging in live cells with high signal-to-noise ratio. The synthesis of bench-stable CinNapht-F has been optimized and can be reproduced on a large scale, making it an easy-to-store starting material that can be used at will to prepare new molecular imaging tools., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Specific knowledge on the distribution of anthrax, a zoonosis caused by Bacillus anthracis , in Southeast Asia, including Vietnam, remains limited. In this study, we describe disease incidence and spatial distribution of human and livestock anthrax using spatially smoothed cumulative incidence from 2004 to 2020 in Cao Bang province, Vietnam. We employed the zonal statistics routine a geographic information system (GIS) using QGIS, and spatial rate smoothing using spatial Bayes smoothing in GeoDa. Results showed higher incidence of livestock anthrax compared with human anthrax. We also identified co-occurrence of anthrax in humans and livestock in northwestern districts and the province center. Livestock anthrax vaccine coverage was <6% and not equally distributed among the districts of Cao Bang province. We provide implications for future studies and recommend improving disease surveillance and response through data sharing between human and animal health sectors.

The generation of enantiodivergent biocatalysts for C-H oxyfunctionalizations is ever more important in modern synthetic chemistry. Here, we have applied the FuncLib algorithm based on phylogenetic and Rosetta calculations to design a diverse repertoire of active, stable, and enantiodivergent fungal peroxygenases. 24 designs, each carrying 4-5 mutations in the catalytic core, were expressed functionally in yeast and benchmarked against characteristic model compounds. Several designs were active and stable in a range of temperature and pH, displaying unprecedented enantiodivergence, changing regioselectivity from alkyl to aromatic hydroxylation, and increasing catalytic efficiencies up to 10-fold, with 15-fold improvements in total turnover numbers over the parental enzyme. We find that this dramatic functional divergence stems from beneficial epistasis among the mutations and an extensive reorganization of the heme channel. Our work demonstrates that FuncLib can rapidly design highly functional libraries enriched in enantioselective peroxygenases not seen in nature for a range of biotechnological applications.

Mathematical modeling is a promising tool for better understanding of cellular processes. In recent years, the development of coarse-grained models has gained attraction since these simple models are able to capture and describe a broad range of growth conditions. Coarse-grained models often comprise only two cellular components, a low molecular component as representative for central metabolism and energy generation and a macromolecular component, representing the entire proteome. A framework is presented that presents a strict mass conservative model for bacterial growth during a biotechnological production process. After providing interesting properties for the steady-state solution, applications are presented 1) for a production process of an amino acid and 2) production of a metabolite from central metabolism., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Doan, Hoang, Heins and Kremling.)

Biotechnological production processes are sustainable approaches for the production of biobased components such as amino acids for food and feed industry. Scale-up from ideal lab-scale bioreactors to large-scale processes is often accompanied by loss in productivity. This may be related to population heterogeneities of cells originating from isogenic cultures that arise due to dynamic non-ideal conditions in the bioreactor. To better understand this phenomenon, deeper insights into single-cell physiologies in bioprocesses are mandatory before scale-up. Here, a triple reporter strain (3RP) was developed by chromosomally integrating the fluorescent proteins mEmerald, CyOFP1, and mTagBFP2 into the L-phenylalanine producing Escherichia coli strain FUS4 (pF81 kan ) to allow monitoring of growth, oxygen availability, and general stress response of the single cells. Functionality of the 3RP was confirmed in well-mixed lab-scale fed-batch processes with glycerol as carbon source in comparison to the strain without fluorescent proteins, leading to no difference in process performance. Fluorescence levels could successfully reflect the course of related process state variables, revealed population heterogeneities during the transition between different process phases and potentially subpopulations that exhibit superior process performance. Furthermore, indications were found for noise in gene expression as regulation strategy against environmental perturbation., Competing Interests: The authors have declared no conflicts of interest., (© 2022 The Authors. Engineering in Life Sciences published by Wiley‐VCH GmbH.)

Flow cytometry and its technological possibilities have greatly advanced in the past decade as analysis tool for single cell properties and population distributions of different cell types in bioreactors. Along the way, some solutions for automated real-time flow cytometry (ART-FCM) were developed for monitoring of bioreactor processes without operator interference over extended periods with variable sampling frequency. However, there is still great potential for ART-FCM to evolve and possibly become a standard application in bioprocess monitoring and process control. This review first addresses different components of an ART-FCM, including the sampling device, the sample-processing unit, the unit for sample delivery to the flow cytometer and the settings for measurement of pre-processed samples. Also, available algorithms are presented for automated data analysis of multi-parameter fluorescence datasets derived from ART-FCM experiments. Furthermore, challenges are discussed for integration of fluorescence-activated cell sorting into an ART-FCM setup for isolation and separation of interesting subpopulations that can be further characterized by for instance omics-methods. As the application of ART-FCM is especially of interest for bioreactor process monitoring, including investigation of population heterogeneity and automated process control, a summary of already existing setups for these purposes is given. Additionally, the general future potential of ART-FCM is addressed., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Engineering in Life Sciences published by Wiley‐VCH GmbH.)

Fungal unspecific peroxygenases (UPOs) are emergent biocatalysts that perform highly selective C-H oxyfunctionalizations of organic compounds, yet their heterologous production at high levels is required for their practical use in synthetic chemistry. Here, we achieved functional expression of two new unusual acidic peroxygenases from Candolleomyces ( Psathyrella ) aberdarensis ( Pab UPO) in yeasts and their production at a large scale in a bioreactor. Our strategy was based on adopting secretion mutations from an Agrocybe aegerita UPO mutant, the PaDa-I variant, designed by directed evolution for functional expression in yeast, which belongs to the same phylogenetic family as Pab UPOs, long-type UPOs, and shares 65% sequence identity. After replacing the native signal peptides with the evolved leader sequence from PaDa-I, we constructed and screened site-directed recombination mutant libraries, yielding two recombinant Pab UPOs with expression levels of 5.4 and 14.1 mg/liter in Saccharomyces cerevisiae. These variants were subsequently transferred to Pichia pastoris for overproduction in a fed-batch bioreactor, boosting expression levels up to 290 mg/liter, with the highest volumetric activity achieved to date for a recombinant peroxygenase (60,000 U/liter, with veratryl alcohol as the substrate). With a broad pH activity profile, ranging from pH 2.0 to 9.0, these highly secreted, active, and stable peroxygenases are promising tools for future engineering endeavors as well as for their direct application in different industrial and environmental settings. IMPORTANCE In this work, we incorporated several secretion mutations from an evolved fungal peroxygenase to enhance the production of active and stable forms of two unusual acidic peroxygenases. The tandem-yeast expression system based on S. cerevisiae for directed evolution and P. pastoris for overproduction on an ∼300-mg/liter scale is a versatile tool to generate UPO variants. By employing this approach, we foresee that acidic UPO variants will be more readily engineered in the near future and adapted to practical enzyme cascade reactions that can be performed over a broad pH range to oxyfunctionalize a variety of organic compounds.

Six-membered-diaza ring of cinnoline has been fused on naphthalimide dye to give a donor-acceptor system called CinNapht. This red shifted fluorophore, that can be synthesised in gram scale, exhibits a large Stoke shift and a fluorescence quantum yield up to 0.33. It is also characterized by a strong solvatochromic effect from green to red emission as well and can be used for bio-imaging., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objective: Geraniol, a fragrance of great importance in the consumer goods industry, can be glucosylated by the UDP-glucose-dependent glucosyltransferase VvGT14a from Vitis vinifera, yielding more stable geranyl glucoside. Escherichia coli expressing VvGT14a is a convenient whole-cell biocatalyst for this biotransformation due to its intrinsic capability for UDP-glucose regeneration. The low water solubility and high cytotoxicity of geraniol can be overcome in a biphasic system where the non-aqueous phase functions as an in situ substrate reservoir. However, the effect of different process variables on the biphasic whole-cell biotransformation is unknown. Thus, the goal of this study was to identify potential bottlenecks during biotransformation with in situ geraniol supply via isopropyl myristate as second non-aqueous phase., Results: First, insufficient UDP-glucose supply could be ruled out by measurement of intracellular UDP-glucose concentrations. Instead, oxygen supply was determined as a bottleneck. Moreover, the formation of the byproduct geranyl acetate by chloramphenicol acetyltransferase (CAT) was identified as a constraint for high product yields. The use of a CAT-deficient whole-cell biocatalyst prevented the formation of geranyl acetate, and geranyl glucoside could be obtained with 100% selectivity during a biotransformation on L-scale., Conclusion: This study is the first to closely analyze the whole-cell biotransformation of geraniol with Escherichia coli expressing an UDP-glucose-dependent glucosyltransferase and can be used as an optimal starting point for the design of other glycosylation processes.

Threats to biodiversity are well documented. However, to effectively conserve species and their habitats, we need to know which conservation interventions do (or do not) work. Evidence-based conservation evaluates interventions within a scientific framework. The Conservation Evidence project has summarized thousands of studies testing conservation interventions and compiled these as synopses for various habitats and taxa. In the present article, we analyzed the interventions assessed in the primate synopsis and compared these with other taxa. We found that despite intensive efforts to study primates and the extensive threats they face, less than 1% of primate studies evaluated conservation effectiveness. The studies often lacked quantitative data, failed to undertake postimplementation monitoring of populations or individuals, or implemented several interventions at once. Furthermore, the studies were biased toward specific taxa, geographic regions, and interventions. We describe barriers for testing primate conservation interventions and propose actions to improve the conservation evidence base to protect this endangered and globally important taxon., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Institute of Biological Sciences.)

Polydiacetylene micelles were assembled from four different cationic amphiphiles and photopolymerized to reinforce their architecture. The produced micelles were systematically investigated, in interaction with siRNAs, for intracellular delivery of the silencing nucleic acids. The performances of the carrier systems were rationalized based on the cell penetrating properties of the micelles and the nature of their cationic complexing group, responsible for efficient siRNA binding and further endosomal escape., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objective: Rates of total knee arthroplasty (TKA) and total hip arthroplasty (THA) remain high for patients with rheumatoid arthritis (RA), who are at risk of flaring after surgery. We aimed to describe rates, characteristics, and risk factors of RA flare within 6 weeks of THA and TKA., Methods: Patients with RA were recruited prior to elective THA and TKA surgery and prospectively followed. Clinicians evaluated RA clinical characteristics 0-2 weeks before and 6 weeks after surgery. Patients answered questions regarding disease activity including self-reported joint counts and flare status weekly for 6 weeks. Per standard of care, biologics were stopped before surgery, while glucocorticoids and methotrexate (MTX) were typically continued. Multivariable logistic regression was used to identify baseline characteristics associated with postsurgical RA flares., Results: Of 120 patients, the mean age was 62 years and the median RA duration 14.8 years. Ninety-eight (82%) met 2010/1987 American College of Rheumatology/European League Against Rheumatism criteria, 53 (44%) underwent THA (and the rest TKA), and 61 (51%) were taking biologics. By 6 weeks, 75 (63%) had flared. At baseline, flarers had significantly higher disease activity (as measured by the 28-joint Disease Activity Score), erythrocyte sedimentation rate, C-reactive protein, and pain. Numerically more flarers used biologics, but stopping biologics did not predict flares, and continuing MTX was not protective. A higher baseline disease activity predicted flaring by 6 weeks (OR 2.12, p = 0.02)., Conclusion: Flares are frequent in patients with RA undergoing arthroplasty. Higher baseline disease activity significantly increases the risk. Although more patients stopping biologics flared, this did not independently predict flaring. The effect of early postsurgery flares requires further study.