Immunization with a peptide mimicking lipoteichoic acid induces memory B cells in BALB/c mice.

BACKGROUND: There is an urgent clinical need for developing novel immunoprophylaxis and immunotherapy strategies against Staphylococcus aureus (S. aureus). In our previous work, immunization with a tetra-branched multiple antigenic peptide, named MAP2-3 that mimics lipoteichoic acid, a cell wall component of S. aureus, successfully induced a humoral immune response and protected BALB/c mice against S. aureus systemic infection. In this study, we further investigated whether vaccination with MAP2-3 can elicit immunologic memory. METHODS: BALB/c mice were immunized with MAP2-3 five times. After one month of the last vaccination, mice were challenged with heat-killed S. aureus via intraperitoneal injection. After a 7-day inoculation, the percentage of plasma cells, memory B cells, effector memory T cells, and follicular helper T cells were detected by flow cytometry. The levels of IL-6, IL-21, IL-2, and IFN-γ were measured by real-time PCR and ELISA. Flow cytometry results were compared by using one-way ANOVA or Mann-Whitney test, real-time PCR results were compared by using one-way ANOVA, and ELISA results were compared by using one-way ANOVA or student's t-test. RESULTS: The percentage of plasma cells and memory B cells in the spleen and bone marrow from the MAP2-3 immunized mice was significantly higher than that from the control mice. The percentage of effector memory T cells in spleens and lymphoid nodes as well as follicular helper T cells in spleens from the MAP2-3 immunized mice were also higher. Moreover, the levels of IL-6 and IL-21, two critical cytokines for the development of memory B cells, were significantly higher in the isolated splenocytes from immunized mice after lipoteichoic acid stimulation. CONCLUSIONS: Immunization with MAP2-3 can efficiently induce memory B cells and memory T cells.

Sex differences in children's cognitive functions and phthalates exposure: a meta-analysis.

BACKGROUND: Phthalates exposure might affect children's intelligence development. This study aimed to determine (1) whether sex and age affect cognitive function and (2) whether sex differences in cognitive performance are wider with higher phthalate concentrations. METHODS: Data were collected from PubMed (1998-2022), PROQUEST (1997-2022), and SpringerLink (1995-2022). The study followed the PRISMA process. The included articles were followed by PECO framework. The GRADE applied to assess the certainty of evidence. Of 2422 articles obtained, nine were selected using inclusion criteria. The random-effects model was used to estimate the pooled effects. RESULTS: Our meta-regression indicated a significant difference between sex differences with age at phthalate concentration assessment (ß = -0.25; 95% CI = -0.47, -0.03) and MEHP concentration (ß = -0.20; 95% CI = -0.37, -0.03). CONCLUSIONS: The limitation of the current article is it only provides information on intelligence level rather than other aspects of cognitive function. Thus, the sequelae of phthalate exposure on attention and executive function are still unclear. Our analysis shows significant difference between sex differences in cognitive function scores associated with age at phthalate concentration assessment. Girls might be more resilient in cognitive function at a younger age or during lower concentrations of phthalates metabolites. IMPACT: This is the first meta-analysis to evaluate the pooled estimates of sex differences in objective cognitive functions among children with phthalate exposure. The female might be a protective factor when exposed to toxic plasticizers while the concentration is low. This study captures the possible role of sex in cognitive functioning and plasticizer exposure through a meta-analysis of children's sex, cognitive scores, and plasticizer exposure.

Twelve tips for co-production of online learning.

In the digital age, experts in digital learning tools, or learning technologists (LTs), play an increasingly important role in the creation and delivery of online learning in health professions education. However, their expertise in the selection, curation and implementation of digital tools is often underutilized due to imbalanced relationships and lack of effective collaboration between faculty and LTs. Here, we describe how the co-production model can be applied to build equal and synergistic partnerships between faculty and LTs, so as to optimize the use of digital affordances and enhance online learning.

Umpolung Difunctionalization of Carbonyls via Visible-Light Photoredox Catalytic Radical-Carbanion Relay.

The combination of photoredox catalysis with the Wolff-Kishner (WK) reaction allows the difunctionalization of carbonyl groups by a radical-carbanion relay sequence (photo-Wolff-Kishner reaction). Photoredox initiated radical addition to N-sulfonylhydrazones yields α-functionalized carbanions following the WK-type mechanism. With sulfur-centered radicals, the carbanions are further functionalized by reaction with electrophiles including CO2 and aldehydes, whereas CF3 radical addition furnishes a wide range of gem-difluoroalkenes through ß-fluoride elimination of the generated α-CF3 carbanions. More than 80 substrate examples demonstrate the broad applicability of this reaction sequence. A series of investigations including radical inhibition, deuterium labeling, fluorescence quenching, cyclic voltammetry, and control experiments support the proposed radical-carbanion relay mechanism.

The failure of non-invasive prenatal testing due to maternal dermatomyositis.

We experienced a case of a pregnant woman who failed to obtain a result from NIPT, due to the high level of total cell-free DNA. A subsequent ultrasound examination discovered that the fetus had severe intrauterine growth restriction, so the woman decided to abort the baby. At the same time, the woman developed slight swelling and tenderness of the proximal interphalangeal and meta-carpophalangeal joints. At first, these symptoms were not noticed, but, when the pregnant woman was admitted to the hospital, her laboratory tests were seriously abnormal, such as serum lactate dehydrogenase (640U/L), creatine phosphor kinase (4525U/L), kinase isoenzyme MB (170U/L), and a hydroxybutyrate dehydrogenase (398U/L). The patient had no other symptoms at this time. Misoprostol and subsequent forceps curettage were used for the induced abortion, a 167-g female fetus was aborted. Fetal skin tissue was taken for chromosomal microarray analysis (CMA) and placenta (biopsied in four places and tested as two composite samples) were taken for postnatal karyotyping to exclude a confined placental mosaicism, chromosomal microarray analysis of the fetal skin tissue revealed that the karyotype was 46, XX, karyotyping of placenta (100 cells) gave results of 46, XX, no abnormalities were detected. Ten days after induction, the patient had developed progressive symmetric muscle weakness in the proximal extremities. Physical examination revealed Gottron's sign and erythema. A manual muscle test showed weakness of the muscles (4/5) of her proximal extremities. Electromyography showed myogenic impairment. After excluding the possibility of neoplasia, the patient was diagnosed with dermatomyositis.

Caring for patients on home enteral nutrition: Reported complications by home carers and perspectives of community nurses.

AIMS AND OBJECTIVES: To explore the experiences of community nurses and home carers, in caring for patients on home enteral nutrition. BACKGROUND: The number of patients on home enteral nutrition is on the increase due to advancement in technology and shift in focus of providing care from acute to community care settings. METHODS: A mixed-method approach was adopted. (i) A face-to-face survey design was used to elicit experience of carers of patients on home enteral nutrition. (ii) Focus group interviews were conducted with community nurses. RESULTS: Ninety-nine carers (n = 99) were recruited. Patient's mean age that they cared for was aged 77.7 years (SD = 11.2), and they had been on enteral feeding for a mean of 29 months (SD = 23.0). Most were bed-bound (90%) and required full assistance with their feeding (99%). Most were not on follow-up with dietitians (91%) and dentists (96%). The three most common reported gastrointestinal complications were constipation (31%), abdominal distension (28%) and vomiting (22%). Twenty community nurses (n = 20) were recruited for the focus group interviews. Four main themes emerged from the analysis: (i) challenge of accessing allied health services in the community; (ii) shorter length of stay in the acute care setting led to challenges in carers' learning and adaptation; (iii) transition gaps between hospital and home care services; and (iv) managing expectations of family. CONCLUSION: To facilitate a better transition of care for patients, adequate training for carers, standardising clinical practice in managing patients with home enteral nutrition and improving communication between home care services and the acute care hospitals are needed. RELEVANCE TO CLINICAL PRACTICE: This study highlighted the challenges faced by community home care nurses and carers. Results of this study would help to inform future policies and practice changes that would improve the quality of care received by patients on home enteral nutrition.

Synthesis of Polysubstituted Pyrroles through a Formal [4 + 1] Cycloaddition/E1cb Elimination/Aromatization Sequence of Sulfur Ylides and α,ß-Unsaturated Imines.

A reaction sequence comprising a formal [4 + 1] cycloaddition, an E1cb elimination, and an aromatization process is described in this work. By doing so, polysubstituted pyrroles were achieved from easily available chemicals, sulfur ylides, and α,ß-unsaturated imines. This protocol features mild conditions, high efficiency, and wide substrate scopes.

A novel method of self-pulling and latter transected reconstruction in totally laparoscopic total gastrectomy: feasibility and short-term safety.

BACKGROUND: This study depicts a novel reconstruction method of self-pulling and latter transection (SPLT) in totally laparoscopic total gastrectomy (TLTG) and evaluates its feasibility and short-term safety by comparing its surgical and postoperative outcomes with the conventional TLTG. PATIENTS AND METHODS: Forty patients with gastric cancer from June 2014 to December 2015 received SPLT-TLTG. Data of clinicopathologic characteristics, surgical and postoperative outcomes, and follow-up findings in SPLT cases were collected and retrospectively compared with those of conventional TLTG to clarify the clinical benefits. RESULTS: The mean duration of the operation was 179.5 ± 37.7 min in SPLT-TLTG, including 23.2 ± 8.8 min of reconstruction; both were significantly shorter than the conventional TLTG (P = 0.030; P < 0.001). There were no significant differences in blood loss, time of the first flatus and postoperative hospital stays between two groups. SPLT-TLTG developed no complication beyond the conventional TLTG. CONCLUSION: SPLT-TLTG is safe, feasible and minimally invasive. It may serve as a promising procedure for gastric cancer that helps to expand the indication of TLTG to cases with even high level of tumor invasion and requires less in both surgical skills and clinical costs.

A novel method of self-pulling and latter transected delta-shaped Billroth-I anastomosis in totally laparoscopic distal gastrectomy.

BACKGROUND: We developed a modified delta-shaped gastroduodenostomy technique in totally laparoscopic distal gastrectomy. This novel technique, which effectively reduces the required quantity of linear stapler [1-3], was named as self-pulling and latter transected delta-shaped anastomosis (Delta SPLT) [4]. METHODS: Delta SPLT was performed on 15 patients with stage cT1-2 antral cancer. We ligated the duodenum with a rope instead of transecting it and used the ligature rope to pull the duodenum during the whole progress of gastroduodenostomy. When closing the entry hole, the duodenum was transected at the same time, which saved one linear stapler. Data of clinicopathologic characteristics, surgical and postoperative outcomes were collected and expressed as means ± standard deviations. RESULTS: All the operations were successfully performed by using no more than four 60-mm linear staplers. The mean BMI of the patients is 23.0 ± 2.5 kg/m2 (range 17.0-26.0 kg/m2), and duration of the operation was 115.0 ± 33.4 min (range 75-215 min), including 22.3 ± 6.7 min (range 15-35 min) of reconstruction. Mean blood loss was 82.7 ± 71.3 mL (range 10-300 mL), and mean times to first flatus was 2.3 ± 1.1 days (range 1-5 days). A mean number of 27.5 ± 5.4 (range 18-38) lymph nodes was retrieved. Overall postoperative morbidity rate was 6.7% (1/15). There was no anastomosis-related complication, but one case of pneumonia developed on postoperative day (POD) 2 which was successfully managed by conservative methods. Patients were discharged (POD mean 5.8 ± 1.3, range 4-9) when their bowel movements recovered and no discomfort with soft diet was claimed. CONCLUSION: Delta SPLT is a safe and feasible technique and requires less clinical costs.

Brain contusion as the main risk factor of memory or emotional complaints in chronic complicated mild traumatic brain injury.

OBJECTIVE: To investigate the risk factors for memory or emotional complaints in patients with complicated mild traumatic brain injury (mTBI). METHODS: Retrospective analysis of medical records was conducted by physicians in a teaching hospital in Southern Taiwan, and complicated mTBI had been identified by means of computed tomography. Psychological complaints, including problems with memory and emotions, were collected by structured telephone interviews, 10-15 minutes long, and were held with subjects who agreed to participate in our study. Among 327 patients who were injured for more than two years, 190 agreed to join this study (mean age: 41.6 years; male: 60.5%; stably employed: 50.0%). We used demographic data and neurological factors to predict memory or emotional complaints without muscle power or response speed (MEMR) complaints. RESULTS: Only the presence or absence of cerebral contusions predicted memory or emotional complaints without MEMR complaints in different employed status, and the odds ratio was 4.82-13.50 times higher for those with cerebral contusions than for those without. CONCLUSIONS: Cerebral contusions were the primary risk factor for MEMR complaints in chronic complicated mTBI. Early preventive psychological intervention might be necessary for patients with complicated mTBI and cerebral contusions.

Changes of ammonia, urea contents and transaminase activity in the body during aerial exposure and ammonia loading in Chinese loach Paramisgurnus dabryanus.

The Paramisgurnus dabryanus was exposed to 30 mmol L-1 NH4Cl solution and air to assessing the change of body ammonia and urea contents and the activities of alanine aminotransferase (ALT) and aspartate transaminase (AST). After 48 h of ammonia exposure, ammonia concentration in the plasma, brain, liver and muscle were 3.3-fold, 5.6-fold, 3.5-fold and 4.2-fold, respectively, those of the control values. Plasma, brain, liver and muscle ammonia concentrations increased to 2.2-fold, 3.3-fold, 2.5-fold and 2.9-fold, respectively, those of control values in response to 48 h of aerial exposure. Within the given treatment (ammonia or aerial exposure), there was no change in plasma, brain and liver urea concentrations between exposure durations. The plasma ALT activity was significantly affected by exposure time during aerial exposure, while the liver ALT activity was not affected by ammonia or aerial exposure. Exposure to NH4Cl or air had no effect on either plasma or liver AST activity. Our results suggested that P. dabryanus could accumulate quite high level of internal ammonia because of the high ammonia tolerance in its cells and tissues, and NH3 volatilization would be a possible ammonia detoxification strategy in P. dabryanus. Urea synthesis was not an effective mechanism to deal with environmental or internal ammonia problem. The significant increase of ALT activity in plasma during aerial exposure, indicating that alanine synthesis through certain amino acid catabolism may be subsistent in P. dabryanus.

Highly Stereoselective [3+2] Cycloadditions of Chiral Palladium-Containing N(1) -1,3-Dipoles: A Divergent Approach to Enantioenriched Spirooxindoles.

A catalytic asymmetric [3+2] cycloaddition reaction of chiral palladium-containing N(1) -1,3-dipoles with methyleneindolinones has been successfully developed. The reaction allows an efficient construction of 3,3'-pyrrolinyl spirooxindoles with high yields and excellent stereoselectivities (up to 93 % yield, 19:1 d.r. and >99 % ee). A synthetic application of this methodology is demonstrated and a stereocontrol mechanism is proposed.

Formal [3 + 2] Cycloadditions via Indole Activation: A Route to Pyrroloindolines and Furoindolines.

Here, we describe a novel [3 + 2] cycloaddition of 3-substituted indoles with vinyl aziridines and vinyl epoxides that provides a straightforward approach to pyrroloindolines and furoindolines bearing vinyl groups (up to 96% yield and 9:1 dr). In contrary to previous reports involving Lewis acid activation, this work reports successful reactions based on the activation of indole using t-BuOK and BEt3 (triethylborane), thereby preserving the free N-H group on indoles. In addition, a gram-scale reaction and a ring-closing metatheis reaction are performed to provide good demonstrations of the synthetic utility of this approach.

A Copper-Catalyzed Decarboxylative Amination/Hydroamination Sequence: Switchable Synthesis of Functionalized Indoles.

A copper-catalyzed decarboxylative amination/hydroamination sequence of propargylic carbamates with various nucleophiles is described for the first time. It features an earth-abundant metal catalyst, mild reaction conditions, and high efficiency. Further treatments of the resultant key intermediates using an acid or a base in one pot enable the controllable and divergent synthesis of two types of functionalized indoles. Moreover, experiments to demonstrate the synthetic potential of this methodology are performed.

Electroencephalogram valid rate in simple reaction time task as an easy index of children's attention functions.

BACKGROUND: Electroencephalogram (EEG) signal artifacts occur often in children, but an EEG valid rate (VR), constructed by excluding the artifacts, might be meaningful to evaluate children's neuropsychological functions. The aim of this study was to develop an easy screening index, the EEGVR, and to investigate attention function in children using this index. METHODS: The EEG was carried out during a 4 min simple reaction time (SRT) task as standard procedure in 50 children, consisting of 26 with attention-deficit-hyperactivity disorder (ADHD; mean age, 9.8 years; range, 8-11.3 years) and 24 without (mean age, 10.1 years; range, 7.8-12 years). An easy index was derived from the valid rate (VR) of EEG using area under the receiver operating characteristic curve. The index was applied to regroup the 50 children into high VR (HVR) and low VR (LVR) groups, while the Comprehensive Non-verbal Attention Test (CNAT) and four behavioral questionnaires were compared between the two groups in order to investigate the validity of this index. RESULTS: The EEGVR at 75% was optimal to identify HVR and LVR (sensitivity, 0.769; specificity, 0.792). The LVR group had significantly lower scores on both CNAT and the behavioral questionnaires, although the demographic variables and full-scale intelligence quotient (FSIQ) were similar between the two groups. CONCLUSIONS: The EEGVR in an SRT task might be an easy and effective index to screen the attention function of children, and could consequently contribute to the early diagnosis of ADHD.

Elimusertib has Antitumor Activity in Preclinical Patient-Derived Pediatric Solid Tumor Models.

The small-molecule inhibitor of ataxia telangiectasia and Rad3-related protein (ATR), elimusertib, is currently being tested clinically in various cancer entities in adults and children. Its preclinical antitumor activity in pediatric malignancies, however, is largely unknown. We here assessed the preclinical activity of elimusertib in 38 cell lines and 32 patient-derived xenograft (PDX) models derived from common pediatric solid tumor entities. Detailed in vitro and in vivo molecular characterization of the treated models enabled the evaluation of response biomarkers. Pronounced objective response rates were observed for elimusertib monotherapy in PDX, when treated with a regimen currently used in clinical trials. Strikingly, elimusertib showed stronger antitumor effects than some standard-of-care chemotherapies, particularly in alveolar rhabdomysarcoma PDX. Thus, elimusertib has strong preclinical antitumor activity in pediatric solid tumor models, which may translate to clinically meaningful responses in patients.

Passenger Gene Coamplifications Create Collateral Therapeutic Vulnerabilities in Cancer.

DNA amplifications in cancer do not only harbor oncogenes. We sought to determine whether passenger coamplifications could create collateral therapeutic vulnerabilities. Through an analysis of >3,000 cancer genomes followed by the interrogation of CRISPR-Cas9 loss-of-function screens across >700 cancer cell lines, we determined that passenger coamplifications are accompanied by distinct dependency profiles. In a proof-of-principle study, we demonstrate that the coamplification of the bona fide passenger gene DEAD-Box Helicase 1 (DDX1) creates an increased dependency on the mTOR pathway. Interaction proteomics identified tricarboxylic acid (TCA) cycle components as previously unrecognized DDX1 interaction partners. Live-cell metabolomics highlighted that this interaction could impair TCA activity, which in turn resulted in enhanced mTORC1 activity. Consequently, genetic and pharmacologic disruption of mTORC1 resulted in pronounced cell death in vitro and in vivo. Thus, structurally linked coamplification of a passenger gene and an oncogene can result in collateral vulnerabilities. SIGNIFICANCE: We demonstrate that coamplification of passenger genes, which were largely neglected in cancer biology in the past, can create distinct cancer dependencies. Because passenger coamplifications are frequent in cancer, this principle has the potential to expand target discovery in oncology. This article is featured in Selected Articles from This Issue, p. 384.

Neuropsychological Impairments in Patients With Post-traumatic Epilepsy: A Scoping Review.

OBJECTIVES: To date, the research on the prognosis of the neuropsychological function of patients with post-traumatic seizure (PTE) is sparse. This study aimed to systematically map the literature's extent, range, and characteristics regarding PTE and neuropsychological impairments. METHODS: A systematic literature search was conducted in CINAHL, Cochrane, Embase, Medline, PubMed, Scopus, Web of Science, and ScienceDirect databases. The search terms were related to PTE and neuropsychological impairments. RESULTS: This scoping review included seven studies, two of which examined the impact of PTE on neuropsychological outcomes. Among the three studies that used neuropsychological assessments, attention/concentration, and memory were the most frequently assessed domains. Only one study reported a significant difference between PTE and non-PTE patients. The cognitive rating scale findings in the other four studies were similar, indicating that patients with PTE performed worse than those without PTE. CONCLUSIONS: The results of this review suggest that patients with PTE may have neuropsychological function impairments. More attention needs to be paid to older patients and those with higher brain injury and seizure severity. Additional investigation is necessary to determine the clinical characteristics of TBI and PTE and elucidate the relations between PTE and specific neuropsychological domains.

Correlation Among Workplace Burnout, Resilience, and Well-Being in Nursing Staff: A Cross-Sectional Study in Taiwan.

BACKGROUND: Because nurses often work in medical environments characterized by high workloads and high levels of stress and pressure, they are particularly vulnerable to workplace burnout and their well-being may suffer. Related studies on burnout, resilience, and well-being have focused primarily on teachers, social workers, and students, with few studies addressing the situation faced by nursing staff. It is important to understand the factors affecting the well-being of nursing staff. PURPOSE: This study explores the status quo and correlations among nursing-staff demographic characteristics, workplace burnout, well-being-related resilience, and the predictive factors of well-being in nurses. METHODS: A cross-sectional, descriptive, correlational research design and purposive sampling were used in this study. Nursing staff who had worked for more than 6 months at a medical center in central Taiwan were recruited as participants, with data from 289 participants collected. A structured questionnaire was used to collect data on demographic characteristics, workplace burnout, resilience, and well-being. RESULTS: The average scores for workplace burnout, resilience, and well-being were 40.40/(0- to 100-point scale), 26.79/(10- to 50-point scale), and 43.25/(24- to 96-point scale), respectively. The result of the regression analysis explained about 51.6% of the variance in well-being. Furthermore, resilience (28.4%), self-perceived health (14.3%), workplace burnout (4.5%), exercise frequency (1.8%), job title (1.2%), interpersonal pressure relief resilience (0.9%), and marital status (0.5%) were other important predictive factors of well-being in the participants. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Medical institutions should provide appropriate resilience-enhancing countermeasures to reduce workplace burnout as well as pay greater attention to the exercise frequency, self-perceived health, job title, and marital status of their nurses to help them achieve physical, mental, and overall well-being.

Multi-scale dissection of wing transparency in the clearwing butterfly Phanus vitreus.

Optical transparency is rare in terrestrial organisms, and often originates through loss of pigmentation and reduction in scattering. The coloured wings of some butterflies and moths have repeatedly evolved transparency, offering examples of how they function optically and biologically. Because pigments are primarily localized in the scales that cover a colourless wing membrane, transparency has often evolved through the complete loss of scales or radical modification of their shape. Whereas bristle-like scales have been well documented in glasswing butterflies, other scale modifications resulting in transparency remain understudied. The butterfly Phanus vitreus achieves transparency while retaining its scales and exhibiting blue/cyan transparent zones. Here, we investigate the mechanism of wing transparency in P. vitreus by light microscopy, focused ion beam milling, microspectrophotometry and optical modelling. We show that transparency is achieved via loss of pigments and vertical orientation in normal paddle-like scales. These alterations are combined with an anti-reflective nipple array on portions of the wing membrane being more exposed to light. The blueish coloration of the P. vitreus transparent regions is due to the properties of the wing membrane, and local scale nanostructures. We show that scale retention in the transparent patches might be explained by these perpendicular scales having hydrophobic properties.