bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of TGF‐β3 in modulating inflammatory responses and wound healing processes in ischemic ulcers in atherosclerotic patients
Authors: Ma Tian Yi , Tang Shi Lin , Wang Bin , Wang Gan , Sun Chang Ming , Pan Jia Xi , Han Dan Qi , Li Jia Yang , Zhong Jiang Hua
Published: February 2024

Ischemic ulcers pose a multifaceted clinical dilemma for patients with atherosclerosis, frequently compounded by suboptimal wound healing mechanisms. The dual function of Transforming Growth Factor Beta 3 (TGF‐β3) in ischemic ulcer healing is not fully comprehended, despite its involvement in modulating inflammatory responses and tissue regeneration. The main aim of this investigation was to clarify the functions and mechanisms by which TGF‐β3 regulates inflammatory responses and promotes wound healing in patients with ischemic ulcers who have atherosclerosis. Between August 2022 and November 2023, this cross‐sectional investigation was conducted on 428 patients diagnosed with atherosclerotic ischemic ulcers in Haikou, China. The expression and function of TGF‐β3 were examined throughout the different stages of wound healing, including inflammation, proliferation and remodelling. In addition to documenting patient demographics and ulcer characteristics, an analysis was conducted on biopsy samples to determine the expression of TGF‐β3, pro‐inflammatory and anti‐inflammatory markers. A subset of patients were administered topical TGF‐β3 in order to evaluate its therapeutic effects. The expression pattern of TGF‐β3 was found to be stage‐dependent and significant, exhibiting increased levels during the phase of inflammation and reduced activity in subsequent phases. TGF‐β3 levels were found to be greater in ulcers that were larger and deeper, especially in inflammatory phase. TGF‐β3 applied topically induced discernible enhancement in ulcer healing parameters, such as reduction in ulcer depth and size. The therapeutic significance of TGF‐β3 was emphasised due to its twofold function of regulating the inflammatory environment and facilitating the regeneration of damaged tissues. Ischemic ulcer lesion healing is significantly influenced by TGF‐β3, which functions as an anti‐inflammatory and pro‐inflammatory mediator. Its correlation with ulcer characteristics and stages of healing suggests that it may have utility as a targeted therapeutic agent.
Resurrection and redescriptions of nominal species previously regarded as synonyms of Thrissina mystax (Bloch and Schneider, 1801) (Teleostei: Clupeiformes: Engraulidae)
Authors: Hata Harutaka , Lavoué Sébastien
Published: February 2024

Examination of the original descriptions and available type specimens of nominal species previously regarded as synonyms of Thrissina mystax (Bloch and Schneider, 1801), and many non‐type specimens representing an extensive geographic range, confirmed the validities of T. mystax, Thrissina porava (Bleeker, 1849), and Thrissina valenciennesi (Bleeker, 1866). Additionally, Engraulis poorawah Bleeker, 1872, a nominal species previously regarded as a junior synonym of T. mystax, is recognized as a junior synonym of Thrissina malabarica (Bloch, 1795). Diagnoses and detailed color descriptions are given for all of the valid species, in addition to clarification of their taxonomic histories, and neotype designation for T. porava. The phylogenetic relationships among 15 species of Thrissina (including T. porava and T. valenciennesi but not T. mystax) were reconstructed from the mitochondrial cytochrome oxidase I (COI) gene. T. porava and T. valenciennesi were not recovered as a monophyletic group, instead being divergent from each other and the other species of Thrissina by 12.4% and >11.7% mean uncorrected distances, respectively, confirming their reciprocal validity.
Flexural strength of 3D‐printed nanocomposite provisional resins: Impact of SiO2 and ZrO2 nanoparticles and printing orientations in vitro
Authors: AlGhamdi Maram A. , Alatiyyah Fatimah M. , Dawood Zainab H. Al , Alshaikhnasser Farah Y. , Almedarham Rawan F. , Alboryh Shaymaa Y. , Elakel Ahmed , Akhtar Sultan , Khan Soban Q. , Gad Mohammed M.
Published: February 2024

Purpose

The aim of this study was to investigate and compare the influence of zirconium dioxide nanoparticles (ZrO2NPs) and silicon dioxide nanoparticles (SiO2NPs) addition and printing orientation on the flexural strength (FS) of provisional three‐dimensional (3D) printing resins undergoing thermal cycling (TC).

Methods

Three dimensional‐printed resin (NextDent C&B MFH) was used to fabricate 300 bar‐shaped specimens (25 × 2 × 2 mm3). The ZrO2NPs and SiO2NPs specimens were divided into two groups, then subdivided into three groups, based on the nanoparticle concentration (i.e., 0 wt% (original group), 0.5 wt%, and 1 wt%). Each concentration was printed in three printing orientations (0°, 45°, and 90°). The printed specimens were exposed to 5000 cycles of TC, followed by a three‐point bending test to assess the FS. Fracture surface analysis was conducted by using a scanning electron microscope (SEM). For data analysis, ANOVA and Tukey's post hoc were utilized (α = 0.05).

Results

Compared to the original material, the addition of ZrO2NPs and SiO2NPs had a significantly positive impact on the FS, (P > 0.001). After TC, the FS of the original group decreased significantly and had the lowest value. The highest FS value was observed in 1% ZrO2NPs at 0°. Regardless of the nanoparticle concentration, the 0° orientation consistently showed a higher FS, compared to the 45° and 90° orientations. At all orientations (i.e., 0°, 45°, and 90°), the FS significantly increased with the addition of NPs, compared with that of the original material (P > 0.001). TC had a significantly negative effect on the FS of the unmodified groups. However, no significant differences existed in FS among the modified groups after TC.

Conclusion

The addition of SiO2NPs and ZrO2NPs increased the FS of the 3D‐printed provisional resin. Regardless of the nanoparticle concentration, the 0° orientation had the higher FS. TC had an effect on the original resin, whereas it had no significant effect on the nanoparticle‐modified resins. In clinical practice, 3D‐printed provisional nanocomposite resins printed at the 0° orientation could be recommended for long‐term dental provisional restorations.
Do what we did last year, but do not stray too far from the pack: A behavioral public finance approach to municipal cash reserves
Authors: Pierson Kawika , Thompson Jon C. , Thompson Fred
Published: February 2024

We leverage a national panel of US municipalities to show that behavioral finance helps explain the number of months of expenses that municipalities save in cash and investment reserves. We hypothesize that municipal managers may be using numerical anchoring based on historical values to target the number of months of savings to hold and that they may also be engaged in social learning to target months of savings based on the behavior of neighboring municipalities. We test for these effects by combining two innovative techniques, a two‐stage regression designed to test for anchoring of present financial values based on theoretically unimportant historical values, and a measure of the spatial autocorrelation of savings to test for social learning. The results suggest that, in deciding how much to save, municipal managers are influenced by the levels of savings they held in the past and the savings levels of their neighbors, and that they underreact to changes in theoretically relevant economic fundamentals. Further tests also suggest that the smallest cities by population are more influenced by the behavior of their neighbors than their past savings, whereas the largest cities show the opposite result, effectively choosing themselves as their own role models.
Octacalcium phosphate collagen composite for periodontal regeneration in a canine one‐wall intrabony defect
Authors: Yamaki Daichi , Fukuba Shunsuke , Okada Munehiro , Takeuchi Shunsuke , Hoshi Shu , Matsuura Takanori , Iwata Takanori
Published: February 2024

Objective

This study aimed to evaluate the regenerative capacities of octacalcium phosphate collagen composite (OCP/Col) in one‐wall intrabony defects in dogs. The background data discuss the present state of the field: No study has assessed the efficacy of OCP/Col for periodontal regeneration therapy despite the fact that OCP/Col has proved to be efficient for bone regeneration.

Methods

In six beagle dogs, the mandibular left third premolars were extracted 12 weeks before the experimental surgery. Standardized bone defects (5 mm in height and 4 mm in width) were simulated on the distal surface of the second premolars and mesially on the fourth premolars. The defect was filled with either OCP/Col (experimental group) or left empty (control group). Histological and histomorphometric characteristics were compared 8 weeks after surgery.

Results

No infectious or ankylotic complications were detected at any of the tested sites. The experimental group exhibited a significantly greater volume, height, and area of newly formed bone than the control group. The former also showed a greater height of the newly formed cementum than the latter, although the results were not statistically significant. The newly formed periodontal ligaments were inserted into newly formed bone and cementum in the experimental group.

Conclusion

OCP/Col demonstrated high efficacy for bone and periodontal tissue regeneration that can be successfully applied for one‐wall intrabony defects.
Transcutaneous electrical nerve stimulation in the management of restless legs syndrome symptoms: A single‐blind, parallel‐group clinical study
Authors: Şanli Zeynep Selcan , Ortaç Emine Aygül , Binokay Hülya , Aktaş Kübra
Published: February 2024

The aim of this study was to investigate the additional effect of transcutaneous electrical nerve stimulation (TENS) on the control of the symptoms of restless legs syndrome (RLS). A total of 46 randomly selected patients diagnosed with RLS were divided into two groups in a single‐blind study to either receive pramipexole (0.25 mg daily) plus 10 sessions of TENS or only pramipexole (0.25 mg daily) for 4 weeks. The severity of the symptoms was determined according to the International Restless Legs Syndrome Rating Scale (IRLSRS) and the Pittsburgh sleep quality index (PSQI) at the beginning of the treatment, post‐treatment, and at an 8 week follow‐up. A significant time interaction was observed between the groups for all measurement outcomes, revealing differences in favour of the experimental group's IRLSRS and PSQI scores. A notable improvement was also observed in the IRLSRS and PSQI scores in both groups at the end of treatment and during the 8 week follow‐up period. In comparison with pramipexole monotherapy, the results of this study showed that the use of TENS therapy combined with a low dose of pramipexole (0.25 mg daily) is therapeutically beneficial in the treatment of RLS over an 8 week follow‐up period.
Hit‐and‐run or hit‐and‐stay? Unintended effects of a stricter BAC limit
Authors: French Michael T. , Gumus Gulcin
Published: February 2024

Although they comprise a relatively small subset of all traffic deaths, hit‐and‐run (HR) fatalities are both contemptible and preventable. We analyze longitudinal data from 1982 to 2008 to examine the effects of blood alcohol concentration (BAC) laws on HR traffic fatalities. Our results suggest that lower BAC limits may have an unintended consequence of increasing HR fatalities, whereas a similar effect is absent for non‐HR fatalities. Specifically, we find that the adoption of a 0.08 BAC limit is associated to an 8.3% increase in HR fatalities. This unintended effect is more pronounced in urban areas and during weekends, which are typical settings for HR incidents.
Suicide following a conviction, solitary confinement, or transfer in people incarcerated: A comprehensive retrospective cohort study in France, 2017–2020
Authors: Vanhaesebrouck Alexis , Fovet Thomas , Melchior Maria , Lefevre Thomas
Published: February 2024

Introduction

Suicide rates are higher in prison than in the general population in most countries. The proximity of some suicides to prison events has only received little attention in comparative studies. The aim of this study was to assess the relationship between suicide and four prison events: conviction, disciplinary solitary confinement, nondisciplinary solitary confinement and inter‐prison transfer, in a national retrospective cohort study of people in prison.

Methods

All incarcerations in France that occurred during 2017–2020 were eligible. Data were collected from an administrative database of the National Prison Service. Survival bivariate and multivariate analyses were performed with a Cox regression model.

Results

Of 358,522 incarcerations were included, among which 469,348 events and 449 suicides occurred. In multivariate analysis, suicide risk was higher the first day of disciplinary solitary confinement (HR = 42.1 [21.5–82.7] and HR = 119.0 [71.5–197.9], before and after a government decree on the disciplinary system, respectively. It was higher within 2 weeks after a transfer (HR = 3.5 [2.3–5.2])) or entry in nondisciplinary solitary confinement (HR = 6.7 [3.4–13.3]) and lower within 2 weeks after a conviction (HR = 0.6 [0.4–1.0]).

Conclusion

Solitary confinement and transfer were found to be precipitating factors of suicide in people who are incarcerated. These results offer interesting perspectives on prevention.
Anticipation of landing leg masks ankle inversion orientation deficits and peroneal insufficiency during jump landing in people with chronic ankle instability
Authors: Hou Zongchen , Shen Wei , Fong Daniel T. P. , Winter Samantha L.
Published: February 2024

Ankle inversion orientation and peroneal activation insufficiency may contribute to lateral ankle sprains during landing in chronic ankle instability (CAI); however, how anticipation alters these factors is neglected. This study aimed to assess the impact of anticipation on joint orientation and muscle activity during landing in individuals with CAI. Fifteen participants with CAI and 15 healthy participants (control) were recruited to perform single‐leg landings after bilateral countermovement jumps when the landing limb was specified before (planned) or after (unplanned) take‐off. Joint angle (hip, knee, and ankle) and electromyography (gluteus medius, rectus femoris, biceps femoris, gastrocnemius lateral head, tibialis anterior, and peroneal longus) were collected and analyzed with 2 (groups) × 2 (conditions) statistical parametric mapping ANOVA. In the unplanned condition, the CAI group demonstrated a less plantarflexed (maximum difference [MD] = 9.5°, p = 0.047) and more inverted ankle joint (MD = 4.1°, p < 0.001) before ground contact, along with lower peroneal activity at ground contact compared to the control group (MD = 28.9% of peak activation, p < 0.001). No significant differences between groups were observed in the planned condition. In conclusion, anticipation may mask jump landing deficits in people with CAI, including inverted ankle orientation and reduced peroneus longus activity pre‐ and post‐landing, which were observed exclusively in unplanned landings. Clinicians and researchers need to recognize the impact of anticipation on apparent landing deficits and consider the implications for injury prevention and rehabilitation strategies.
“We're gonna get you through it”: The role of bonding social capital in the development of bridging social capital
Authors: Iantosca Megan Holland , Kimelberg Shelley M. , Lewis Danielle V. , Taughrin Ryan J.
Published: February 2024

Many programs that place low‐income students of color in high‐achieving college preparatory high schools seek to nurture bridging social capital, connections across class lines that provide leverage in the process of “getting ahead.” Bonding social capital, which focuses more on emotional support and “getting by,” is frequently characterized as less useful for social mobility. Drawing upon in‐depth interviews with alumni from one such program, we challenge the notion of bridging and bonding social capital as discrete, countervailing forms of social capital, and demonstrate how the two may complement each other. Specifically, we find that bonding social capital served as a critical resource that students drew upon as they navigated their elite high schools in the face of racism and classism. In doing so, this bonding social capital ultimately facilitated the development of bridging social capital by encouraging student persistence at these institutions. Our findings support critiques of traditional accounts of social capital that devalue the capital possessed by marginalized communities and fuel deficit ideologies. Furthermore, they highlight the personal costs that youth may face in the pursuit of bridging capital, complicating the narrative of social mobility as an unmitigated good.
Trust, institutional quality, and the protection of property rights: A cross‐regional study of East Asia and Western countries
Authors: Chung Kee Hoon , Kwon Hyeok Yong
Published: February 2024

Objective

This article explores the conditions under which social trust enhances institutional performance, specifically the protection of property rights in Western versus East Asian countries over time.

Methods

We estimate fixed‐effects panel regression models to test how the relationship between trust and property rights protection is moderated by the quality of political institutions, including state capacity, the legal system, and democracy.

Results

We find that the relationship between social trust and property rights protection is contingent on the quality of political institutions across regions. The quality of the legal system exerts the most pronounced and contrasting effect on the link between social trust and property rights protection in Western and East Asian countries, while the conditional effects of state capacity and democracy are comparatively less pronounced in both regions.

Conclusion

This study contributes valuable insights into the complex interplay between social trust and institutional outcomes in diverse societal contexts.
All politics are national: Partisan defection in national and subnational elections
Authors: Sievert Joel , Banda Kevin K.
Published: February 2024

Objective

While they were once viewed as largely local or candidate‐centered contests, recent American elections have come to be dominated by national forces such as presidential politics and partisanship. Prior research on voter behavior in this new era of nationalized politics, however, has largely focused on more high‐profile contests and has not examined voter decision making across multiple levels of government.

Methods

Our study uses cross‐sectional (2006–2020) survey data from the Cooperative Election Study to explore the determinants of partisan loyalty and defection across both national and subnational American elections.

Results

We find consistent evidence that citizens increasingly rely upon national forces—specifically partisan‐ideological sorting and presidential approval—to make decisions about candidates up and down the ballot. We also find mixed evidence that evaluations of the national economy inform defection behavior.

Conclusion

These findings indicate that the national political forces shape voter behavior in national and subnational contests in effectively identical ways. Thus, the evidence supports the notion that all (electoral) politics are now national.
Characterization of the novel HLA‐B*57:169 allele by next generation sequencing
Authors: Gravante Chris , Berka Yacine , Peters Lindsey , Mancini Shannon , Liacini Abdelhamid
Published: February 2024

HLA‐B*57:169 differs from HLA‐B*57:01:01:12 by one nucleotide substitution at position 2512, codon 320 located in exon 6.
Genomic full‐length sequence of the HLA‐C*07:154 allele was identified by full‐length group‐specific sequencing
Authors: An Run , Jiang Zhi , Zhu YuLi , Jiao Shuxian , Pang Shutao
Published: February 2024

Genomic full‐length sequence of HLA‐C*07:154 was identified by group‐specific sequencing in a Chinese individual.
A single nucleotide substitution in intron 3 generated the novel HLA‐A*11:01:01:68 allele
Authors: Sharma Akanksha , Bagchi Soumita , Barwad Adarsh W. , Agarwal Sanjay Kumar , Kanga Uma
Published: February 2024

HLA‐A*11:01:01:68 differs from HLA‐A*11:01:01:01 by one nucleotide change in intron 3 at position 1474 (G > A).
Characterization of seven novel HLA‐DPA1*01:03:01 non‐coding variants by next‐generation sequencing
Authors: Gil‐Etayo Francisco Javier , Niño Ramírez Jairo Eduardo , Vicente Parra Ariadna , Arroyo‐Sánchez Daniel , Tejeda Velarde Amalia
Published: February 2024

Seven different single nucleotide substitutions in non‐coding regions gave rise to novel HLA‐DPA1*01:03:01 variants.
Identification of the novel HLA‐C*03:132:02 allele in a Chinese individual by next‐generation sequencing
Authors: Wang Ziqing , Sun Yamin , Kang Yiqing , Li Jianbin , Liu Zheng
Published: February 2024

Compared with the HLA‐C*03:132:01 allele, HLA‐C*03:132:02 shows one nucleotide substitution at position 270A>C.
Identification of the novel HLA‐DRB1*14:253 allele by next‐generation sequencing
Authors: Bouthemy Charlène , Cargou Marine , Fort Marylise , Congy‐Jolivet Nicolas
Published: February 2024

HLA‐DRB1*14:253 differs from DRB1*14:54:01 by one nucleotide substitution in codon 233 in exon 5.
Repeat patient testing‐quality control compared to commercial quality control material for the Sysmex XT‐2000iV hematology analyzer in a multi‐site veterinary laboratory
Authors: Daly S. , Rishniw M. , Graham P. A. , Freeman K. P.
Published: February 2024

Background

Quality control material (QCM) for hematology in veterinary laboratories is limited, and repeat patient testing quality control (RPT‐QC) is an alternative method using excess matrix‐specific samples.

Objectives

This study aimed to determine if median differences between RPT‐QC analyses for each time interval for RBC, HGB, HCT, and WBC were the same, determine if unified RPT‐QC limits can be applied to a network of veterinary laboratories, compare the performance of RPT‐QC to commercial QCM for the reference analyzer and evaluate the experience over a 4 month period and design, improve and implement an automated spreadsheet for RPT‐QC data management.

Methods

The potential to unify individual analyzer RPT‐QC limits for red blood cells (RBC), hematocrit (HCT), hemoglobin (HGB), and white blood cells (WBC) on multi‐site Sysmex XT‐2000‐iV analyzers was explored by a difference of means test and confidence interval determination for the median difference for each network analyzer in comparison to the network reference analyzer. User experience of an automated RPT‐QC data management Excel spreadsheet was collected by user feedback during monthly meetings. Numbers of out‐of‐control results and the root causes for these for RPT‐QC were compared against those of a commercial QCM over a 4‐month period.

Results

Differences between individual analyzer RPT‐QC limits were too large to allow for unification of network limits. The automated spreadsheet successfully highlighted out‐of‐control events for RPT‐QC. Trends or shifts were more frequent for commercial QCM based on observed performance and a 1–2.5 s QC rule than for RPT‐QC. Following routine troubleshooting, RPT‐QC out‐of‐control events were resolved with an alternative RPT‐QC sample indicating random error associated with excessive deterioration. Use of an automated spreadsheet for recording RPT‐QC, documentation and troubleshooting of out‐of‐control events, and collating monthly summary calculations were considered an asset in laboratory quality management.

Conclusions

RPT‐QC can be successfully implemented and integrated into a multi‐site veterinary laboratory. Individual analyzer RPT‐QC limit generation is recommended. The deterioration of commercial QCM caused shifts or trends in QC results, which initiated more repeat analyses and investigations than did RPT‐QC.
Blood lactate after pre‐hospital blood transfusion for major trauma by helicopter emergency medical services
Authors: Mitra Biswadev , Talarico Carly S. , Olaussen Alexander , Anderson David , Meadley Ben
Published: February 2024

Background and Objectives

The appropriate use of blood components is essential for ethical use of a precious, donated product. The aim of this study was to report in‐hospital red blood cell (RBC) transfusion after pre‐hospital transfusion by helicopter emergency medical service paramedics. A secondary aim was to assess the potential for venous blood lactate to predict ongoing transfusion.

Materials and Methods

All patients who received RBC in air ambulance were transported to a single adult major trauma centre, had venous blood lactate measured on arrival and did not die before ability to transfuse RBC were included. The association of venous blood lactate with ongoing RBC transfusion was assessed using multi‐variable logistic regression analysis and reported using adjusted odds ratios (aOR). The discriminative ability of venous blood lactate was assessed using area under receiver operating characteristics curve (AUROC).

Results

From 1 January 2016 to 15 May 2019, there were 165 eligible patients, and 128 patients were included. In‐hospital transfusion occurred in 97 (75.8%) of patients. Blood lactate was associated with ongoing RBC transfusion (aOR: 2.00; 95% confidence interval [CI]: 1.36–2.94). Blood lactate provided acceptable discriminative ability for ongoing transfusion (AUROC: 0.78; 95% CI: 0.70–0.86).

Conclusions

After excluding patients with early deaths, a quarter of those who had prehospital RBC transfusion had no further transfusion in hospital. Venous blood lactate appears to provide value in identifying such patients. Lactate levels after pre‐hospital transfusion could be used as a biomarker for transfusion requirement after trauma.
Attosecond-pump attosecond-probe x-ray spectroscopy of liquid water
Authors: Li Shuai , Lu Lixin , Bhattacharyya Swarnendu , Pearce Carolyn , Li Kai , Nienhuis Emily T. , Doumy Gilles , Schaller R. D. , Moeller S. , Lin M.-F. , Dakovski G. , Hoffman D. J. , Garratt D. , Larsen Kirk A. , Koralek J. D. , Hampton C. Y. , Cesar D. , Duris Joseph , Zhang Z. , Sudar Nicholas , Cryan James P. , Marinelli A. , Li Xiaosong , Inhester Ludger , Santra Robin , Young Linda
Published: February 2024

Attosecond-pump/attosecond-probe experiments have long been sought as the most straightforward method for observing electron dynamics in real time. Although there has been much success with overlapped near-infrared femtosecond and extreme ultraviolet attosecond pulses combined with theory, true attosecond-pump/attosecond-probe experiments have been limited. We used a synchronized attosecond x-ray pulse pair from an x-ray free-electron laser to study the electronic response to valence ionization in liquid water through all x-ray attosecond transient absorption spectroscopy (AX-ATAS). Our analysis showed that the AX-ATAS response is confined to the subfemtosecond timescale, eliminating any hydrogen atom motion and demonstrating experimentally that the 1b1splitting in the x-ray emission spectrum is related to dynamics and is not evidence of two structural motifs in ambient liquid water.
Telomerase misbehaves after a breakup
Authors: Arnoult Nausica , Cech Thomas R.
Published: February 2024

Suppressing telomerase action at broken DNA preserves genome integrity
Abundant urinary amino acids activate glutamine synthetase-encoding
glnA
by two different mechanisms in
Escherichia coli
Authors: Urs Karthik , Zimmern Philippe E. , Reitzer Larry
Published: February 2024

Growth of uropathogenic
Escherichia coli
in the bladder induces transcription of
glnA
which codes for the ammonia-assimilating glutamine synthetase (GS) despite the normally suppressive high ammonia concentration. We previously showed that the major urinary component, urea, induces transcription from the Crp-dependent
glnAp1
promoter, but the urea-induced transcript is not translated. Our purpose here was to determine whether the most abundant urinary amino acids, which are known to inhibit GS activity
in vitro
, also affect
glnA
transcription
in vivo
. We found that the abundant amino acids impaired growth, which glutamine and glutamate reversed; this implies inhibition of GS activity. In strains with deletions of
crp
and
glnG
that force transcription from the
glnAp2
and
glnAp1
promoters, respectively, we examined growth and
glnA
transcription with a
glnA-gfp
transcriptional fusion and quantitative reverse transcription PCR with primers that can distinguish transcription from the two promoters. The abundant urinary amino acids stimulated transcription from the
glnAp2
promoter in the absence of urea but from the
glnAp1
promoter in the presence of urea. However, transcription from
glnAp1
did not produce a translatable mRNA or GS as assessed by a
glnA-gfp
translational fusion, enzymatic assay of GS, and Western blot to detect GS antigen in urea-containing media. We discuss these results within the context of the extremely rapid growth of uropathogenic
E. coli
in urine, the different factors that control the two
glnA
promoters and possible mechanisms that either overcome or bypass the urea-imposed block of glutamine synthesis during bacterial growth in urine.

IMPORTANCE

Knowledge of the regulatory mechanisms for genes expressed at the site of infection provides insight into the virulence of pathogenic bacteria. During urinary tract infections—most often caused by
Escherichia coli
—growth in urine induces the
glnA
gene which codes for glutamine synthetase. The most abundant urinary amino acids amplified the effect of urea which resulted in hypertranscription from the
glnAp1
promoter and, unexpectedly, an untranslated transcript.
E. coli
must overcome this block in glutamine synthesis during growth in urine, and the mechanism of glutamine acquisition or synthesis may suggest a possible therapy.
Ammonia stress-induced heat shock factor 1 enhances white spot syndrome virus infection by targeting the interferon-like system in shrimp
Authors: Wang Xin-Xin , Zhang Hui , Gao Jie , Wang Xian-Wei
Published: February 2024

Disease emergence is the consequence of host-pathogen-environment interactions. Ammonia is a key stress factor in aquatic environments that usually increases the risk of pathogenic diseases in aquatic animals. However, the molecular regulatory mechanisms underlying the enhancement of viral infection following ammonia stress remain largely unknown. Here, we found that ammonia stress enhances white spot syndrome virus infection in kuruma shrimp (
Marsupenaeus japonicus
) by targeting the antiviral interferon-like system through heat shock factor 1 (Hsf1). Hsf1 is an ammonia-induced transcription factor. It regulates the expression of
Cactus
and
Socs2
, which encode negative regulators of NF-κB signaling and Jak/Stat signaling, respectively. By inhibiting these two pathways, ammonia-induced Hsf1 suppressed the production and function of MjVago-L, an arthropod interferon analog. Therefore, this study revealed that Hsf1 is a central regulator of suppressed antiviral immunity after ammonia stress and provides new insights into the molecular regulation of immunity in stressful environments.

IMPORTANCE

Ammonia is the end product of protein catabolism and is derived from feces and unconsumed foods. It threatens the health and growth of aquatic animals. In this study, we demonstrated that ammonia stress suppresses shrimp antiviral immunity by targeting the shrimp interferon-like system and that heat shock factor 1 (Hsf1) is a central regulator of this process. When shrimp are stressed by ammonia, they activate Hsf1 for stress relief and well-being. Hsf1 upregulates the expression of negative regulators that inhibit the production and function of interferon analogs in shrimp, thereby enhancing white spot syndrome viral infection. Therefore, this study, from a molecular perspective, explains the problem in the aquaculture industry that animals living in stressed environments are more susceptible to pathogens than those living in unstressed conditions. Moreover, this study provides new insights into the side effects of heat shock responses and highlights the complexity of achieving cellular homeostasis under stressful conditions.
The phosphatidylinositol-5′ phosphatase synaptojanin1 limits integrin-mediated invasion of
Staphylococcus aureus
Authors: Shi Yong , Muenzner Petra , Schanz-Jurinka Stefanie , Hauck Christof R.
Published: February 2024

The gram-positive bacterium
Staphylococcus aureus
can invade non-professional phagocytic cells by associating with the plasma protein fibronectin to exploit host cell integrins. Integrin-mediated internalization of these pathogens is facilitated by the local production of phosphatidylinositol-4,5-bisphosphate (PI-4,5-P
2
) via an integrin-associated isoform of phosphatidylinositol-5′ kinase. In this study, we addressed the role of PI-4,5-P
2
-directed phosphatases on internalization of
S. aureus
. ShRNA-mediated knockdown of individual phosphoinositide 5-phosphatases revealed that synaptojanin1 (SYNJ1) is counteracting invasion of
S. aureus
into mammalian cells. Indeed, shRNA-mediated depletion as well as genetic deletion of synaptojanin1 via CRISPR/Cas9 resulted in a gain-of-function phenotype with regard to integrin-mediated uptake. Surprisingly, the surface level of integrins was slightly downregulated in Synj1-KO cells. Nevertheless, these cells showed enhanced local accumulation of PI-4,5-P
2
and exhibited increased internalization of
S. aureus
. While the phosphorylation level of the integrin-associated protein tyrosine kinase FAK was unaltered, the integrin-binding and -activating protein talin was enriched in the vicinity of
S. aureus
in synaptojanin1 knockout cells. Scanning electron microscopy revealed enlarged membrane invaginations in the absence of synaptojanin1 explaining the increased capability of these cells to internalize integrin-bound microorganisms. Importantly, the enhanced uptake by Synj1-KO cells and the exaggerated morphological features were rescued by the re-expression of the wild-type enzyme but not phosphatase inactive mutants. Accordingly, synaptojanin1 activity limits integrin-mediated invasion of
S. aureus
, corroborating the important role of PI-4,5-P
2
during this process.

IMPORTANCE

Staphylococcus aureus
, an important bacterial pathogen, can invade non-professional phagocytes by capturing host fibronectin and engaging integrin α5β1. Understanding how
S. aureus
exploits this cell adhesion receptor for efficient cell entry can also shed light on the physiological regulation of integrins by endocytosis. Previous studies have found that a specific membrane lipid, phosphatidylinositol-4,5-bisphosphate (PIP2), supports the internalization process. Here, we extend these findings and report that the local levels of PIP2 are controlled by the activity of the PIP2-directed lipid phosphatase Synaptojanin1. By dephosphorylating PIP2 at bacteria-host cell attachment sites, Synaptojanin1 counteracts the integrin-mediated uptake of the microorganisms. Therefore, our study not only generates new insight into subversion of cellular receptors by pathogenic bacteria but also highlights the role of host cell proteins acting as restriction factors for bacterial invasion at the plasma membrane.
Unravelling HetC as a peptidase-based ABC exporter driving functional cell differentiation in the cyanobacterium
Nostoc
PCC 7120
Authors: Rachedi Raphaël , Risoul Véronique , Foglino Maryline , Aoudache Yanis , Lang Kevin , Champ Stéphanie , Kaplan Elise , Orelle Cédric , Douzi Badreddine , Jault Jean-Michel , Latifi Amel
Published: February 2024

The export of peptides or proteins is essential for a variety of important functions in bacteria. Among the diverse protein-translocation systems, peptidase-containing ABC transporters (PCAT) are involved in the maturation and export of quorum-sensing or antimicrobial peptides in Gram-positive bacteria and of toxins in Gram-negative organisms. In the multicellular and diazotrophic cyanobacterium
Nostoc
PCC 7120, the protein HetC is essential for the differentiation of functional heterocysts, which are micro-oxic and non-dividing cells specialized in atmospheric nitrogen fixation. HetC shows similarities to PCAT systems, but whether it actually acts as a peptidase-based exporter remains to be established. In this study, we show that the N-terminal part of HetC, encompassing the peptidase domain, displays a cysteine-type protease activity. The conserved catalytic residues conserved in this family of proteases are essential for the proteolytic activity of HetC and the differentiation of heterocysts. Furthermore, we show that the catalytic residue of the ATPase domain of HetC is also essential for cell differentiation. Interestingly, HetC has a cyclic nucleotide-binding domain at its N-terminus which can bind ppGpp
in vitro
and which is required for its function
in vivo
. Our results indicate that HetC is a peculiar PCAT that might be regulated by ppGpp to potentially facilitate the export of a signaling peptide essential for cell differentiation, thereby broadening the scope of PCAT role in Gram-negative bacteria.

IMPORTANCE

Bacteria have a great capacity to adapt to various environmental and physiological conditions; it is widely accepted that their ability to produce extracellular molecules contributes greatly to their fitness. Exported molecules are used for a variety of purposes ranging from communication to adjust cellular physiology, to the production of toxins that bacteria secrete to fight for their ecological niche. They use export machineries for this purpose, the most common of which energize transport by hydrolysis of adenosine triphosphate. Here, we demonstrate that such a mechanism is involved in cell differentiation in the filamentous cyanobacterium
Nostoc
PCC 7120. The HetC protein belongs to the ATP-binding cassette transporter superfamily and presumably ensures the maturation of a yet unknown substrate during export. These results open interesting perspectives on cellular signaling pathways involving the export of regulatory peptides, which will broaden our knowledge of how these bacteria use two cell types to conciliate photosynthesis and nitrogen fixation.
Successful use of sclerotherapy in giant supraglottic vascular malformation
Authors: Tsang William , Meghji Sheneen , Masterson Liam , Fish Brian
Published: February 2024

A young male patient presented with an incidental finding of a large supraglottic vascular lesion. The lesion was initially noted during intubation 4 years ago. Although originally listed for elective excision, there was a significant delay and at the time of surgery, the lesion proved too large to remove and a significant threat to the patient’s airway. An emergency tracheostomy was performed, followed by two consecutive treatments with sclerotherapy agents to reduce the size of the lesion. It was then successfully excised using a Thunderbeat ultrasound and bipolar dissection and cautery device.
Double-chambered right ventricle in a patient with pulmonary atresia and ventricular septal defect
Authors: Jayaprasad Narayanapillai , Madhavan Suresh
Published: February 2024

Double-chambered right ventricle is a rare form of right ventricular outflow tract obstruction caused by anomalous hypertrophy of muscle bundles in right ventricle. Cases most often occur in children and rarely in adults. Most cases (80–90%) are associated with ventricular septal defect. We describe a case of pulmonary atresia and ventricular septal defect with double-chambered right ventricle. The interesting clinical findings, ECG, echocardiography and angiocardiography features are described here.
Neonatal hypocalcaemic seizures unmasking asymptomatic maternal primary hyperparathyroidism
Authors: Kaur Ramandeep , Choudhary Sushil Kumar , Singh Arunkumarendu , Gupta Neeraj
Published: February 2024

Hypocalcaemia is a common cause of neonatal seizures. Here, we present a breastfed neonate with smooth perinatal transition and no family history of seizures presenting at 3 weeks with recurrent multifocal clonic seizures. On evaluation, the neonate was found to have low iCa and total calcium. 25-hydroxy vitamin D (25(OH)D) level was low and intact parathyroid hormone (iPTH) was inappropriately normal. The maternal evaluation revealed high calcium and low phosphate levels. iPTH was very high and 25(OH)D was very low in the mother. Sestamibi scan showed a left inferior parathyroid adenoma in the mother. Maternal primary hyperparathyroidism causing hypercalcaemia can suppress parathyroid activity in the fetus, resulting in inappropriate parathyroid response to hypocalcaemia after birth causing recurrent hypocalcaemic seizures. So neonatal hypocalcaemic seizures need careful evaluation of the neonate and the mother at times and can help both mother and neonate.
Experience of patients and physiotherapists within the AFTER pilot randomised trial of two rehabilitation interventions for people aged 50 years and over post ankle fracture: a qualitative study
Authors: Tutton Elizabeth , Gould Jenny , Lamb Sarah E , Costa Matthew L , Keene David J
Published: February 2024

Objectives

To explore patient and staff experience of best-practice rehabilitation advice (one session of face-to-face self-management advice with up to two additional optional sessions) compared with progressive functional exercise (up to six sessions of face-to-face physiotherapy) after ankle fracture.

Design

The study drew on phenomenology using interviews and a focus group.

Setting

Participants were from three NHS Trusts in England, UK.

Participants

A purposive sample of 20 patients with ankle (malleolar) fractures from the Ankle Fracture Treatment: Enhancing Rehabilitation-pilot trial (now completed) were interviewed (median 50 min) from May 2019 to January 2020. They were 6 months post injury, over 50 years of age, (median 66, 12 females) and had received surgical or non-surgical treatment (seven internal fixation surgery, seven close contact casting, six walking boot). A focus group of five physiotherapists who had provided the study interventions (2.5 hours) was undertaken.

Results

The findings show the acceptability of both interventions through the themes, ‘being helped’ (for patients) and ‘developing expertise’ (for staff) with subthemes of choosing and progressing. Progressive exercise added value with a perceived increase in strength, motion, ability to undertake activities and continued use of the workbook. Both staff and patients valued physiotherapy expertise demonstrated through interpersonal skills, advice, individualised exercise plans and active monitoring of progression. Best practice advice was particularly helpful in the early stages of recovery and with the use of mobility aids.

Conclusion

Both interventions were acceptable but progressive exercise was highly valued by patients. Developing expertise through experiential learning enabled staff to facilitate progression. Adjustments to the workbook and the addition of exercises for continued recovery in the best practice advice would enhance a future study. Research during treatment provision may provide further insights into the challenges of facilitating progression of exercise.

Trial registration

ISRCTN16612336;AFTER-pilot trial).
Intravenous immunoglobulin treatment in childhood encephalitis (IgNiTE): a randomised controlled trial
Authors: Hill Matilda , Iro Mildred , Sadarangani Manish , Absoud Michael , Cantrell Liberty , Chong Kling , Clark Christopher , Easton Ava , Gray Victoria , Kneen Rachel , Lim Ming , Liu Xinxue , Pike Michael , Solomon Tom , Vincent Angela , Willis Louise , Yu Ly-Mee , Pollard Andrew J
Published: February 2024

Objective

To investigate whether intravenous immunoglobulin (IVIG) improves neurological outcomes in children with encephalitis when administered early in the illness.

Design

Phase 3b multicentre, double-blind, randomised placebo-controlled trial.

Setting

Twenty-one hospitals in the UK.

Participants

Children aged 6 months to 16 years with a diagnosis of acute or subacute encephalitis, with a planned sample size of 308.

Intervention

Two doses (1 g/kg/dose) of either IVIG or matching placebo given 24–36 hours apart, in addition to standard treatment.

Main outcome measure

The primary outcome was a ‘good recovery’ at 12 months after randomisation, defined as a score of≤2 on the Paediatric Glasgow Outcome Score Extended.

Secondary outcome measures

The secondary outcomes were clinical, neurological, neuroimaging and neuropsychological results, identification of the proportion of children with immune-mediated encephalitis, and IVIG safety data.

Results

18 participants were recruited from 12 hospitals and randomised to receive either IVIG (n=10) or placebo (n=8) between 23 December 2015 and 26 September 2017. The study was terminated early following withdrawal of funding due to slower than anticipated recruitment, and therefore did not reach the predetermined sample size required to achieve the primary study objective; thus, the results are descriptive. At 12 months after randomisation, 9 of the 18 participants (IVIG n=5/10 (50%), placebo n=4/8 (50%)) made a good recovery and 5 participants (IVIG n=3/10 (30%), placebo n=2/8 (25%)) made a poor recovery. Three participants (IVIG n=1/10 (10%), placebo n=2/8 (25%)) had a new diagnosis of epilepsy during the study period. Two participants were found to have specific autoantibodies associated with autoimmune encephalitis. No serious adverse events were reported in participants receiving IVIG.

Conclusions

The IgNiTE (ImmunoglobuliN in the Treatment of Encephalitis) study findings support existing evidence of poor neurological outcomes in children with encephalitis. However, the study was halted prematurely and was therefore underpowered to evaluate the effect of early IVIG treatment compared with placebo in childhood encephalitis.

Trial registration number

Clinical Trials.govNCT02308982; ICRCTN registryISRCTN15791925.
Protection against Incidences of Serious Cardiovascular Events Study with daily fish oil supplementation in dialysis patients (PISCES): protocol for a randomised controlled trial
Authors: Lok Charmaine E , Hemmelgarn Brenda R , Moist Louise M , Polkinghorne Kevan , Tomlinson George , Tonelli Marcello
Published: February 2024

Introduction

Patients with kidney failure with replacement therapy (KFRT) suffer premature cardiovascular (CV) mortality and events with few proven pharmacological interventions. Omega-3 polyunsaturated essential fatty acids (n-3 PUFAs) are associated with a reduced risk of CV events and death in non-dialysis patients and in patients with established CV disease but n-3 PUFAs have not been evaluated in the high risk KFRT patient population.

Methods and analysis

This multicentre randomised, placebo controlled, parallel pragmatic clinical trial tests the hypothesis that oral supplementation with n-3 PUFA, when added to usual care, leads to a reduction in the rate of serious CV events in haemodialysis patients when compared with usual care plus matching placebo. A target sample size of 1100 KFRT patients will be recruited from 26 dialysis units in Canada and Australia and randomised to n-3 PUFA or matched placebo in a 1:1 ratio with an expected intervention period of at least 3.5 years. The primary outcome to be analysed and compared between intervention groups is the rate of all, not just the first, serious CV events which include sudden and non-sudden cardiac death, fatal and non-fatal myocardial infarction, stroke, and peripheral vascular disease events.

Ethics and dissemination

This study has been approved by all institutional ethics review boards involved in the study. Participants could only be enrolled following informed written consent. Results will be published in peer-reviewed journals and presented at scientific and clinical conferences.

Trial registration number

ISRCTN00691795