bluuebunny/crossref_metadata_2025 huggingface dataset:
Negative pressure wound therapy reduces the incidence of postoperative wound dehiscence and surgical site infections after total knee arthroplasty in patients with obesity
Authors: Song Qi-Chun , Li Dong , Zhao Yan , Zhang Guang-Yang , Shang Dong-Long , Fan Li-Hong , Dang Xiao-Qian
Published: July 2022

Obesity is a risk factor for total knee arthroplasty (TKA). Wound dehiscence and surgical site infections (SSIs) are the main complications of TKA in patients with obesity. They can profoundly affect patients because they often require readmission, additional surgical interventions, lengthy intravenous antibiotic administration, and delayed rehabilitation. Negative pressure wound therapy (NPWT) exposes the wound site to negative pressure, resulting in the improvement of blood supply, removal of excess fluid, and stimulation of cellular proliferation of granulation tissue. This study aims to assess the incidence of wound dehiscence and SSIs in patients with obesity undergoing TKA after the routine use of NPWT. This sduty enrolled adult patients with obesity who underwent TKA within 8 years. A total of 360 adult patients with obesity (NPWT: 150, non-NPWT: 210) underwent TKA, and the baseline characteristics were similar between the 2 groups. Compared with the non-NPWT group, the NPWT group had a 50% lower incidence of wound dehiscence (3.33% vs 9.52%; P < .05) and a significantly lower incidence of SSIs (11.33% vs 25.24%; P < .05), including prosthetic joint infection (4.0% vs 10.0%; P < .05) and superficial wound infection (7.33% vs 15.24%; P < .05). In addition, the NPWT group had a lower need to return to the operating room for new interventions for any reason (2.67% vs 9.05%; P = .0107) than the non-NPWT group. Conventional incision NPWT can significantly reduce the incidence of wound dehiscence and SSIs in patients with obesity after TKA.
Consumption of fruits, vegetables, and legumes are associated with overweight/obesity in the middle- and old-aged Chongqing residents: A case-control study
Authors: Wu E , Ni Juntao , Zhou Wei , You Leiying , Tao Lin , Xie Tian
Published: July 2022

This study aimed to investigate the association of dietary habits with the risk of overweight/obesity among middle-and-old-aged Chongqing residents and also to examine the joint effects of behavioral lifestyles, dietary habits, and overweight/obesity.

In this case-control study, age (±3 years), sex, and time of physical exercise matched 979 overweight/obesity residents, and 979 normal weight residents were recruited.

A validated questionnaire was used to collect participants’ information. Conditional logistic regression analysis was performed to determine the adjusted odds ratios (ORs) and 95% CIs of dietary habits and lifestyles associated with overweight/obesity risk.

Overweight/obesity was defined as body mass index (BMI) ≥ 24 kg·m−2, and normal weight was defined as 18.5 ≤ BMI < 24 kg·m−2.

The multivariate-adjusted models showed the weekly intake frequency of fruits 0–1 (day/week) (OR = 1.79, 95% CI = 1.04–3.10), and legumes 0–1 (day/week) (OR = 2.45, 95% CI = 1.28–4.67), as well as the weekly intake percentage of vegetables ≥ 15% (OR = 2.44, 95% CI = 1.04–5.71) were associated with a higher risk of overweight/obesity. Besides, there were joint effects of lifestyles (smoking or drinking) and dietary habits on overweight/obesity risk (P for interaction < 0.05).

The consumption of vegetables, fruits, legumes, and the joint effects of behavioral habits (smoking or drinking) may modify the risk of being overweight/obese. It is essential to consume fruits and legumes at least 2 days/week, quit smoking, and stop consuming alcohol to avoid overweight/obesity among middle-aged and elderly people in Chongqing, China.
Increased severity of complications after therapeutic ERCP in geriatric patients with chronic pancreatitis: An observational study
Authors: Guo Ji-Yao , Zhu Jia-Hui , Pan Jun , Wang Yuan-Chen , Qian Yang-Yang , Hu Liang-Hao , He Chao-Hui , Zou Wen-Bin
Published: July 2022

Studies of therapeutic endoscopic retrograde cholangiopancreatography (ERCP) in geriatric patients have mainly examined patients with biliary diseases, rather than chronic pancreatitis (CP). This study aimed to evaluate the safety and success rate of therapeutic ERCP in geriatric patients with CP.

The medical records of patients with CP aged over 65 years (group A) were retrospectively collected in a tertiary hospital from January 2013 to December 2018. Sex-matched CP patients under 65 years (group B) were randomly selected into the control group (matching ratio = 1:2). The success rate and the complication rate of therapeutic ERCP in 2 groups were compared. The risk factors for post-ERCP pancreatitis were investigated by univariate and multivariate analyses.

A total of 268 ERCPs were performed in 179 patients of group A and 612 ERCPs in 358 patients of group B. The success rate of ERCP in group A was similar to that of group B (92.16% vs 92.32%; P = .936). The overall incidence of post-ERCP complications was 7.09% (19/268) and 5.72% (35/612) in group A and B, respectively (P = .436). However, geriatric patients had a significantly increased occurrence of moderate to severe complications (2.61% vs 0.16%; P = .002). Female gender (odds ratio [OR] = 3.40; P = .046), pancreas divisum (OR = 7.15; P = .049), dorsal pancreatogram (OR = 7.40; P = .010), and lithotripsy (OR = 0.15; P = .016) were significantly associated with risk of post-ERCP pancreatitis in geriatric patients.

Therapeutic ERCP is safe and feasible in elderly patients with CP. However, occurrence of moderate to severe complications after ERCP increased in geriatric patients.
Association of TLR3 gene 1377C/T (rs3775290) and TLR7 gene C/G (rs3853839) polymorphism with hand, foot, and mouth disease caused by human enterovirus 71 infection susceptibility and severity in the Chinese Han population: A meta-analysis of case-control studies
Authors: Tian Haokun , Xu Weikai , Wen Lequan , Tang Lirui , Zhang Xinyuan , Song Tiangang , Yang Changsen
Published: July 2022

Background:

Several case-control studies have been conducted on the relationship between rs3775290 C/T and rs3853839 C/G single nucleotide polymorphisms of the Toll-like receptor (TLR) gene and hand, foot, and mouth disease (HFMD) susceptibility and severity. This meta-analysis aimed to offer a systemic review of HFMD susceptibility and severity among the Chinese Han population associated with the C/T (rs3775290) polymorphism of the TLR3 gene or C/G (rs3853839) polymorphism of the TLR7 gene.

Methods:

A computer search was conducted using PubMed, Web of Science, Embase, CNKI, CBM, VIP, and WanFang databases. The time ranges were from database establishment to 30/7/2021. Articles selected according to the inclusion and exclusion criteria underwent data extraction and methodological quality evaluation. RevMan 5.4 and Stata 16.0 were adopted for meta-analysis, and the incorporated odds ratio (OR) values and 95% confidence intervals (CIs) were calculated. Sensitivity and publication bias assessments were performed.

Results:

8 articles with 9 studies were selected. Among them, there were 858 cases and 577 controls in TLR3 rs3775290 studies as well as 2151 cases and 1554 controls in TLR7 rs3853839 studies. Regarding rs3775290 of TLR3, susceptibilities of the severe type of T-possessing individuals were larger than those of C-possessing individuals [OR = 1.34, 95%CI (1.10, 1.64), P = .004]. The susceptibility of individuals with the severe TT genotype was 1.61 times that of individuals with the CC genotype [95%CI (1.07, 2.43), P=0.02], while susceptibility to HFMD was not influenced by the genotype. In terms of the rs3853839 of the TLR7 gene, C allele carriers have a higher risk of developing HFMD than G allele carriers. The susceptibility to HFMD in CC+CG individuals was 1.24 times than that in GG individuals [95%CI (1.07, 1.43), P = .004]. However, no relationship was found between this polymorphism and severity of the severe type. No significant publication bias was observed in this study.

Conclusions:

rs3775290 (C/T) of TLR3 is associated with susceptibility to the severe type, whereas rs3853839 (C/G) of TLR7 is associated with susceptibility to HFMD. However, owing to the limited quantity and quality of the research, the aforementioned conclusions are yet to be justified by more high-quality research.
Results of intravitreal dexamethasone implant (Ozurdex®) for retinal vascular diseases with macular edema: An observational study of real-life situations
Authors: Jirarattanasopa Pichai , Jiranoppasakdawong Sakunjanut , Ratanasukon Mansing , Bhurayanontachai Patama , Dangboon Wantanee
Published: July 2022

To evaluate the efficacy of intravitreal dexamethasone implants (Ozurdex®) for the treatment of macular edema (ME) associated with retinal vascular diseases in real-life situations.

This retrospective study included patients with ME associated with retinal vascular occlusion (RVO) or diabetic macular edema (DME) treated with dexamethasone implants. Demographic data, best-corrected visual acuity (BCVA), and central retinal thickness (CRT) at baseline and at 1, 3, and 6 months postoperatively were collected and analyzed, and the adverse events were recorded.

Forty-four eyes, 42 patients were included in the study. The mean logMAR BCVA improved from 0.79 ± 0.38 at baseline to 0.60 ± 0.34 (P < 0.001), 0.72 ± 0.38 (P = .002), and 0.72 ± 0.37 (P = .002) at 1, 3, and 6 months, respectively. The CRT decreased from 526.70 ± 159.58 µm at baseline to 279 ± 66.23, 422.91 ± 206.99, and 350.23 ± 151.51 µm at 1, 3, and 6 months, respectively (P < 0.001, all visits). The average number of injections was 1.43 ± 0.5. Nineteen eyes (43.18%) received second injections at an interval of 4.20 ± 0.61 months. The mean logMAR BCVA was greater in RVO than in DME patients and in treatment-naïve eyes than in previously treated ones. The baseline CRT of the reinjection group was significantly higher than that of the single-injection group for both the RVO (P < 0.001) and DME groups (P = .002). Nine eyes (20.45%) with increasing intraocular pressure (IOP) were well controlled with medication, and cataract progression was observed in five eyes (21.73%) during follow-up.

The dexamethasone implant was effective for the treatment of macular edema secondary to RVO and DME in terms of visual acuity and CRT improvement over 6 months. The visual acuity was greater in the RVO and treatment-naïve eyes. Reinjection may be associated with a high baseline CRT. The increase in the occurrence of IOP and cataract progression was similar to that reported in previous studies.
Benefits of esmolol in adults with sepsis and septic shock: An updated meta-analysis of randomized controlled trials
Authors: Zhang Jing , Chen Chun , Liu Yi , Yang Yi , Yang Xiaolei , Yang Jin
Published: July 2022

Background:

Sepsis affects millions of patients annually, resulting in substantial health and economic burdens globally. The role of esmolol potentially plays in the treatment of sepsis and septic shock in adult patients remains controversial.

Methods:

We undertook a systematic search of PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases from their inception to May 12, 2022, for randomized controlled trials that evaluated the efficacy of esmolol for sepsis and septic shock. A random-effects meta-analysis was performed. Two investigators independently screened articles, extracted data, and assessed the quality of included studies.

Results:

Eight studies from 7 randomized controlled trials were included in our meta-analysis of 503 patients with sepsis and/or septic shock. Compared with standard treatment, esmolol significantly decreased 28-day mortality (risk ratio 0.68, 95% confidence interval [CI] 0.52–0.88; P = .004), heart rate (standardized mean difference [SMD] −1.83, 95% CI −2.95 to −0.70, P = .001), tumor necrosis factor-a (SMD −0.48, 95% CI −0.94 to −0.02, P = .04), and the troponin I level (SMD −0.59, 95% CI −1.02 to −0.16, P = .008) 24 hours after treatment. No significant effect was found in terms of length of intensive care unit stay; mean arterial pressure, lactic acid, central venous pressure, or central venous oxygen saturation, interleukin 6, or white blood cell levels; stroke volume index; or the PaO2/FiO2 ratio.

Conclusions:

Esmolol treatment may be safe and effective in decreasing 28-day mortality, controlling heart rate, and providing cardioprotective function, but has no effect on lung injury in patients with sepsis or septic shock after early fluid resuscitation. Improvement in cardiac function may be related to changes in serum inflammatory mediators. No significant adverse effects on tissue perfusion and oxygen utilization were observed.
Analysis of preanalytical errors in a clinical chemistry laboratory: A 2-year study
Authors: Alcantara Jerold C. , Alharbi Bandar , Almotairi Yasser , Alam Mohammad Jahoor , Muddathir Abdel Rahim Mahmoud , Alshaghdali Khalid
Published: July 2022

Patient safety and medical diagnosis of patients are mainly influenced by laboratory results. The present study aimed to evaluate the errors in the preanalytical phase of testing in a Clinical Chemistry diagnostic laboratory.

A review was conducted at the Clinical Chemistry Laboratory of a hospital in Saudi Arabia from January 2019 to December 2020. Using the laboratory information system, the data of all canceled tests and requests were retrieved and evaluated for preanalytical errors.

A total of 55,345 laboratory test requests and samples from different departments were evaluated for preanalytical errors. An overall rate of 12.1% (6705) was determined as preanalytical errors. The occurrence of these errors was found to be highest in the emergency department (21%). The leading preanalytical errors were nonreceived samples (3.7%) and hemolysis (3.5%). The annual preanalytical errors revealed an increasing rate in outpatient and inpatient departments, while a decreasing rate was observed in the emergency department. An increased rate of errors was also noted for the 2-year study period from 11.3% to 12.9%.

The preanalytical phase has a significant impact on the quality of laboratory results. The rate of error in the study was high and the leading causes were nonreceived samples and hemolysis. An increased occurrence of hemolyzed samples in the outpatient department was noted. Enhanced educational efforts emphasizing specimen quality issues and training in sample collection among hospital staff must be carried out.
Effectiveness and safety of Korean medicine treatment based on the clinical practice guidelines in patients with acute peripheral facial palsy: A protocol for a multicenter, prospective, observational study
Authors: Lim Hyewon , Lee Yoonji , Lee Suji , Kim Yong-Suk
Published: July 2022

Introduction:

Peripheral facial palsy (PFP) results in weakness or paralysis of the affected side of the face. In Korea, there is a high demand for Korean medicine treatment for PFP. The clinical practice guidelines (CPGs) of Korean medicine for facial palsy were developed; however, there remains insufficient evidence to support the effectiveness and safety of Korean medicine treatment. Thus, this study aimed to evaluate the effectiveness and safety of Korean medicine treatment based on the CPGs in patients with acute PFP.

Methods:

This is a multicenter, prospective, observational study. The participants will be recruited from one Korean medicine hospital and eight Korean medicine clinics. The participants will receive Korean medicine treatments based on the CPGs, fill in survey questionnaires, and undergo electrophysiologic testing. The changes in House-Brackmann (H-B) grade, movement of the lip and eye, symptoms related to or accompanied by facial palsy, Facial Disability Index, EuroQol 5-dimension 5-level (EQ-5D-5L), and EuroQol Visual Analogue Scale (EQ-VAS), and the results of electromyography (EMG), electroneurography (ENoG), and Blink Reflex test will be analyzed. For the safety analysis, adverse events will be recorded, and for the feasibility analysis, the results of the Was It Worth It questionnaire will be assessed.

Conclusion:

We expect to draw real-world clinical data on the effectiveness and safety of Korean medicine treatment based on the CPGs in patients with acute PFP from this study. It would be the basis for complementing and improving the CPGs and provide the basis of clinical and policy decision-making.

Trial registration:

This study was approved by the Institutional Review Board of Kyung Hee University Korean Medicine Hospital (2021-06-005-001), and registered with the Korean Clinical Trial Registry (CRIS), Republic of Korea (KCT0006562).
Effects on BBPS score with bowel preparation time and dosage
Authors: Lu Wei , Zhou Kena , Cai Congbo , He Yi , Jiang Honggang , Li Xinke
Published: July 2022

Background:

To evaluate the effects on the Boston Bowel Preparation Scale (BBPS) score with different bowel preparation times and dosages.

Methods:

Six hundred patients who underwent colonoscopy in the Endoscopy Center of Ningbo No.9 Hospital in 2021 were recruited and randomly assigned to 3 groups: Group A: “4-hour 1 + 2L” bowel preparation regimen; Group B: “6-hour 1 + 2L” bowel preparation regimen; and Group C: “4-hour 0 + 2L” bowel preparation regimen. BBPS score among these groups is compared and analyzed in the Statistical Product and Service Solutions software.

Results:

There was no difference in baseline characteristics among the three groups of patients (P > .05). There was no significant difference in the BBPS score between Group B and Group C, whereas the BBPS score in Group A was significantly higher than that in Groups B and C (P < .05).

Conclusion:

The “4-hour 1 + 2L” bowel preparation regimen can obtain higher BBPS score for colonoscopy, which is suggested to be the optimal plan for colonoscopy patients of the time and dosage. Definitely, higher BBPS score can improve the quality of colonoscopy diagnosis and treatment consequence.
Moving Toward a Safer Health Care Facility: Improving Patient Identification at a Public Hospital in Saudi Arabia
Authors: AlYaqoub Fatemah , AlMubarak Sama'a H.
Published: July 2022

Background and Objectives:

Patient misidentification errors continue to represent a significant risk to patients, health care staff, and hospitals. The study's purpose was to present a successful quality improvement project implemented in a public hospital in Saudi Arabia. The project focused on increasing staff's compliance with and awareness of the hospital's patient identification policy to thus reducing the number of patient misidentification-related incidents.

Methods:

Through a quality improvement project, we employed FOCUS PDSA to address the issue of patient misidentification at outpatient departments. A total of 640 staff members participated in the educational program including physicians, nurses, receptionists, radiologists, physiotherapists, and laboratory staff. Collected data included measures of compliance and awareness levels as well as patient misidentification incidents, before and after the project. Statistical analysis was conducted to measure significant differences in the study indicators before and after the project.

Results:

Results from the post-project assessment revealed that the project was successful in achieving its objectives. The overall compliance rate and awareness level increased from 59% to 78% and from 75% to 90%, respectively. Improvement in the levels of compliance and awareness was statistically significant. The average number of patient misidentification errors also reduced after the project's implementation with an average of 3 errors per month. The mean difference of patient misidentification errors before and after the project was significant (P < .01).

Conclusion:

This project demonstrated how quality improvement projects can be used to address a critical issue such as patient misidentification. The project furthers efforts made by national and international agencies to improve patient safety. It also highlights the importance of continuous education and training to ensure compliance with patient identification policies that ultimately contributes to a safer hospital environment.
An indolent presentation of brain abscess due to a slow growing organism
Authors: Molai Mariya , Ivan Monica , Bahl Anuj
Published: July 2022

Propioni bacterium propionicum is an anaerobic gram positive bacteria. It’s rarely described as to cause brain abscess. We report the isolation of this organism from a brain abscess and emphasise the problems associated with it’s diagnosis. A 62 year old lady with a history of acromegaly underwent emergency surgery for recurrent pituitary lesion felt to be apoplexy. Four weeks later she presented with headache and confusion. Co morbidities included autoimmune diseases on long term steroids and previous use of immunosuppressants. Clinical examination showed neck stiffness. Brain MRI demonstrated an enhancing lesion in the fourth ventricle causing secondary obstructive hydrocephalus requiring endoscopic third ventriculostomy. Blood tests, CSF analysis and whole body PET scan were unable to differentiate between infection and malignancy. Excision of the lesion was felt very high risk as deep in the tectal area. A sporadic trial of antibiotics, high dose steroids and immunotherapy was tried. Patient developed worsening headache with progression of the lesion. Underwent craniotomy and pus was found which isolated P. propionicum sensitive to penicillin and betalactams. Treated with intravenous meropenem for a year. There was significant reduction in the size of the abscess and hydrocephalus on brain MRI at 8 months post-diagnosis. P. propionicum has been isolated and associated with lesions of the lacrimal glands, lung and abdomen. We could find only two case reports of brain abscess due to P. propionicum. Identification of P.propionicum in the microbiology laboratory can be difficult requiring anaerobic growth conditions and extended cultures. Treatment is prolonged antimicrobial therapy.
Prediction and Assessment of Potential Microbial Substrate Utilisation Among More Recently Identified Health-Associated Gut Taxa
Authors: Lordan Cathy , Thapa Dinesh , Walsh Aaron , Ross Paul , Cotter Paul
Published: July 2022

The contribution of the gut microbiota to health and disease is becoming ever more apparent in the last number of years, due to developments in DNA sequencing technology and more well-defined cultivation techniques. This has resulted in the identification of health-promoting bacteria. Until recently, prebiotics, non-digestible food substrates which are selectively utilised by beneficial bacteria, were employed with a view to increasing the growth of well-established health promoting bacteria, namely Lactobacillus and Bifidobacterium. However, other beneficial bacteria recently revealed may also be targeted to enhance their growth as they establish themselves as the next generation of health-promoting microbes. These include anaerobes such as Akkermansia muciniphila, Faecalibacterium prausnitziiand Eubacterium rectale. Identification of growth substrates/bioactives through the analysis of genome sequence data can aid in elucidating which substrates may best enhance the growth of these microbes which are often difficult to grow.

The phenotypic microbial trait analyser, Traitar, can predict 67 phenotypes based on the genome sequence inputted. Some of these traits include substrates that could potentially be utilised by the bacteria. Another tool, CarveMe, which has been created with the aim of making metabolic modelling more user-friendly, was also used with the same genomes. A select number of substrates identified in both tools have been chosen to be evaluated in vitroin order to establish the accuracy of these predictive tools as well as giving an indication as to how these beneficial microbes can be modulated through dietary components.
Variability in oxygen tolerance among bacterial strains associated with the normal intestinal microbiota
Authors: Pridmore Andrew , Austin Charlotte
Published: July 2022

Anaerobic incubation methods are widely used to cultivate pathogenic anaerobes, but recent years have seen increased interest in potentially therapeutic species originating from the normal intestinal microbiota. We compared the abilities of selected anaerobic pathogens, “normal microbiota” and more recently characterized potentially therapeutic strains to grow on agar at 37°C in the presence of increasing oxygen concentrations, using a variable atmosphere workstation to control oxygen concentration in increments of 0.1%. In initial screening with a high inoculum of 105 to 106 cfu on streak plates, Bacteroides fragilis and Clostridioides difficile strains grew in the presence of up to 2.4% v/v oxygen. Bifidobacterium, Fusobacterium and Finegoldia strains tolerated 0.5 – 1.0% and Eggerthella lenta tolerated 0.1%. Strains of Roseburia, Alistipes, Blautia and Faecalibacterium grew only in strictly anaerobic conditions (<0.01% oxygen) and not in 0.1% oxygen. For strains tolerating >0.1% oxygen in initial experiments, percentage recoveries of smaller inocula (100 – 300 cfu on surface spread plates) were determined in atmospheric oxygen concentrations increasing by 0.1% increments, in comparison with strictly anaerobic colony counts. In 2.0% v/v oxygen, inoculum recovery for 2 × B. fragilis and 1 × C. difficile, was >90%, while recovery of a second C. difficile strain was 25%. For F. magna, inoculum recovery ranged from approximately 100% in 0.1% oxygen to <1% in 0.5% oxygen. These findings demonstrate the variable oxygen tolerance of obligately anaerobic bacteria and emphasize the need for stringent anaerobiosis when culturing the more recently characterized strains currently being developed as live biotherapeutic products.
Antimicrobial Susceptibility Patterns of Anaerobic Bacteria at an Irish University Hospital over the past Decade
Authors: Ali Saied , McNicholas Sinead
Published: July 2022

Background

Various studies have demonstrated poor outcomes in infections caused by anaerobic bacteria due to inappropriate therapy, directly due to emergence of resistant strains. To date there is a paucity of available data on antimicrobial resistance trends of anaerobic bacteria among the Irish population, and our study aims to determine such patterns among isolates processed at our institution over the previous decade.

Methodology

Selected anaerobic bacteria isolated from clinical specimens processed at our laboratory from January 2010 to January 2020 inclusive were collected and studied. Bacteria were identified using MALDI-TOF, with VITEK and E-tests for antimicrobial susceptibility testing. Data was processed through WHONET.

Results

A total of 2098 clinically significant anaerobic bacterial isolates were reviewed during the study period; with the majority of isolates being Bacteroides spp (32.79%, n=688) and Clostridium spp (18.68%, n=392). Bacteroides spp and Prevotella spp were unsurprisingly highly penicillin-resistant at 98.8% (n=680) and 77% (n=114) respectively. Resistance rates against metronidazole were expectedly high amongst Propionibacterium spp (100%, n=341), Actinomyces spp (98.8%, n=79), Lactobacillus spp (59.7%, n=95) and Bifidobacterium spp (53.8%, n=7); whilst remaining anaerobes were largely susceptibility. All isolates were particularly susceptible to co-amoxiclav, piperacillin-tazobactam and meropenem. Clindamycin exhibited a more variable susceptibility pattern, from 6.7% resistance in Staphylococcus saccharolyticus to 81.1% resistance in Prevotella spp.

Conclusion

Metronidazole and beta-lactams remain highly efficacious against the majority of anaerobic isolates reviewed, and remain the backbone of empiric therapy in suspected infections. However, it remains important for periodic surveillance of resistance trends.
Intragenic complementation in the protein kinase domain in Ire1
Authors: Obidan Amnah
Published: July 2022

In eukaryotic cells, secretory and transmembrane proteins fold in the endoplasmic reticulum (ER) before they exit the ER. Accumulation of unfolded proteins activatesIre1 to promote the unfolded protein response (UPR). In the yeast Saccharomyces cerevisiae, activation of Ire1 leads tosplicing of the mRNA for the transcription factor Hac1. Wehave usedb-galactosidase reporter assaysto demonstrateexpression of a UPRE-lacZreporter genethat is positively regulated by the Ire1–Hac1 signalling pathway. In this study, the protein kinase domain was subjected to mutations to alter the catalytic aspartate D797 and lysine K799, which interacts with the terminal phosphate group of ATP, to alanine. Also, point mutations in the Mg+2coordinating loop converted asparagine N802 and aspartic acid D828 to alanine. The expression of theUPRE-lacZreporter gene in all single mutants K799, N802 and D797 was decreased compared to WT-Ire1. Under conditions of various ER stress inducing drugs the ability of the D797A mutant strain to survive was reduced in growth assays compared to other mutants in theMg+2 coordinating loop and catalytic domain. D797-Ire1 mutant has less inb-galactosidase activity, survival of ER stress and HAC1 splicing. Expression of Ire1 carrying double mutations D797A-N802A increasedb-galactosidase activity significantly and restored growth compared to the single mutant D797A-Ire1. WT and protein kinase mutants express to the same level. This study suggeststhat introducing a second mutation such as K799A-Ire1 or N802A-Ire1 to the single mutant D797A-Ire1, restores signaling activity of Ire1.
Virulence traits and differential translocation of gut-derived Candida albicans
Authors: Devlin Edward , Munro Carol , MacCallum Donna , Gratz Silvia
Published: July 2022

Candida albicansis an opportunistic pathogenic yeast commonly found as part of the gut microbiome, which is thought to be the major reservoir of C. albicans in humans. The ability of C. albicans to adhere to, invade and damage epithelium, along with subsequent escape from the gut lumen into the bloodstream, can lead to life-threatening disseminated fungal infections. Examining the interactions of C. albicans with the intestinal epithelial barrier is vital to understanding its ability to disseminate and cause systemic infections.

A set of seven C. albicans strains (six of gut origin: one healthy donor, one cancer patient, one Crohn’s disease patient and three unknown health status; alongside ‘non-gut’ reference strain SC5314) was profiled for virulence traits. C. albicans strains were profiled for biofilm formation (crystal violet staining), hyphal formation (microscopy) and cytotoxicity (lactate dehydrogenase release; during coculture with confluent Caco-2 gut epithelial cells). Additionally, the ability of C. albicans strains to translocate across epithelial cell layers was assessed during coculture with differentiated Caco-2 monolayers on Transwell™ permeable supports.

Common virulence traits of hyphal formation and cytotoxicity were reduced in gut C. albicanscompared to non-gut reference strain SC5314, while biofilm formation compared to SC5314 was variable. Translocation assays revealed that gut strains of C. albicans are capable of translocating across Caco-2 epithelial cell layers in greater numbers than non-gut reference strain SC5314, with the highest levels of translocation observed from a Crohn’s disease isolate. These insights suggest that gut-specific adaptations may influence luminal escape and pathogenicity of C. albicans.
Microfluidics for single-cell noise measurements in budding yeast
Authors: Reed Alan , McCarthy John
Published: July 2022

The combination of microfluidics and time-lapse microscopy is a powerful one, with the potential for the generation of time-series data for single-cell measurements across a whole population of cells. This project aims to employ these tools for the development of technologies and strategies that facilitate the study of stochastic events at the single-cell level. A key focus of the work is the development of microfluidic and image analysis techniques.

Such developments within this project are being applied to study the specific example of noise within the expression of the yeast GCN4 transcriptional regulator. This is activated during amino acid starvation, through a novel post-transcriptional regulatory system. The majority of research into gene expression noise thus far has focused on transcriptional noise, so the impact of post-transcriptional regulation on noise is relatively poorly understood.

Biological systems show many apparently deterministic behaviours at the macroscopic level, but their underlying mechanisms are often stochastic in nature. Noise in gene expression generates heterogeneity across clonal cell populations, and is an important factor in many cellular processes (e.g. circadian rhythms). Even within the well-known “repressilator” synthetic gene circuit, noise had a significant impact on the circuit output. An appreciation of stochasticity in gene expression is therefore crucial for a complete understanding of biology, and will also be essential for the successful design of future synthetic biological systems.
PRS genes, a paradigm for gene duplication and its potential for yeast research?
Authors: Murdoch Emily , Ugbogu Eziuche , Schweizer Lilian , Schweizer Michael
Published: July 2022

TheS. cerevisiaegenome contains five highly homologous PRS genes, each capable of encoding PRPP (phosphoribosyl-pyrophosphate) synthetase, a key enzyme essential for the synthesis of purine and pyrimidine nucleotides. PRS1andPRS5may have arisen from the prototype Prs-encoding genes, PRS2, PRS3andPRS4by duplication followed by acquisition of non-homologous regions (NHRs), shown to link primary metabolism with intracellular signalling. ThePRSgenes are highly conserved from yeast to human. We have created genocopies in PRS1 associated with the human neuropathies, Arts syndrome and CMTX5 which caused increased caffeine sensitivity and elevated Rlm1 expression in the mutated strains. The insertions in Prs1 and Prs5 serve as a physical link to the cell wall integrity (CWI) pathway and explain why cell viability requires specific heterodimers for the provision of PRPP and the maintenance of CWI integrity. The interaction between Prs1 and Mpk1/Slt2, a component of the CWI pathway was demonstrated by immunoprecipitation. Prs3 contains a NLS (nuclear localisation site), deletion of which causes caffeine sensitivity, reduced Rlm1 expression and loss of the Prs1/Prs3 heterodimer. The contribution of Prs5 to CWI is shown by increased phosphorylation of Mpk1/Slt2 following mutation of the three phosphosites located within NHR5-2. We now intend to investigate the signalling pathway connecting the conserved master regulator TOR (target of rapamycin) with PRPP synthetase, thus adding a new dimension to the application of yeast research in the discovery of novel therapeutic targets for the treatment of human neuropathies, CMTX5 and Arts syndrome.
CNN and transfer learning-based classification model for automated cow’s feeding behaviour recognition from accelerometer data
Authors: Bloch Victor , Frondelius Lilli , Arcidiacono Claudia , Mancino Massimo , Pastell Matti
Published: July 2022

Due to technological developments, wearable sensors for monitoring farm animal behaviour have become cheaper, with longer life and more accessible for small farms and researchers. In this study, an acceleration measuring tag connected by BLE for monitoring behaviour of dairy cows was used. An optimal CNN-based model for the feeding behaviour classification was trained and the training process was analysed considering training dataset and the use of transfer learning. A classifier based on a neural network was trained by acceleration data collected in a research barn. Based on a dataset including 33.7 cow*days (21 cow recorded during 1-3 days) of labelled data and an additional free access dataset with similar acceleration data, a classifier with F1=93.9% was developed. The optimal classification window size was 90s. In addition, the influence of the training dataset size on the classifier accuracy was analysed for different neural networks using the transfer learning technique. During increasing of the training dataset size, the rate of the accuracy improvement decreased, and, starting from a specific point, the use of additional training data can be impractical. Relatively high accuracy was achieved with few training data when the classifier was trained using randomly initialised model weights, and higher accuracy was achieved when transfer learning was used. These findings can be used for estimation of the necessary dataset size for training neural network classifiers intended for other environments and conditions.

Highlights

CNN cow feeding behaviour classifier was optimised for neck tags.

Transfer learning technique significantly improves accuracy of CNN.

Relation between the training dataset size and CNN accuracy was estimated.

NN trained by one dataset can be inapplicable for others.

BLE tags measuring acceleration transferred data in real time.
Robust capability of renal tubule fatty acid uptake from apical and basolateral membranes in physiology and disease
Authors: Kawakami Ryo , Hanaoka Hirofumi , Kanai Ayaka , Obinata Hideru , Nakano Daisuke , Ikeuchi Hidekazu , Matsui Miki , Matsuzaki Toshiyuki , Tanaka Rina , Sunaga Hiroaki , Goto Sawako , Matsui Hiroki , Koitabashi Norimichi , Saegusa Keiko , Yokoyama Tomoyuki , Hiromura Keiju , Nishiyama Akira , Saito Akihiko , Yanagita Motoko , Ishii Hideki , Kurabayashi Masahiko , Iso Tatsuya
Published: July 2022

Excess lipid accumulation is associated with obesity-related chronic kidney disease, but the mechanisms of fatty acid (FA) uptake have been poorly understood. To this end, we investigated how FAs are taken up by tubular epithelial cells (TECs) in mice by using in vivo FA tracing and histological methods. Immunohistochemistry showed that CD36, which is a well-known FA transporter, was abundantly expressed on the basolateral side of proximal TECs (PTECs). The uptake of 125I-BMIPP (a radiolabeled FA tracer) was significantly reduced in CD36-knockout kidneys at 1 min after injection. In vivo imaging with multiphoton microscopy revealed that BODIPY-C12 (a fluorescence-labeled FA tracer) accumulated on both the basolateral and apical sides of PTECs. Numerous lipid droplets accumulated in PTECs after accelerated lipolysis. Furthermore, PTEC-specific injury via diphtheria toxin (DT) injection in transgenic mice expressing the DT receptor resulted in a compensatory increase in lipid accumulation in downstream TECs. Importantly, urinary FAs were undetectable, even in mice and humans with remarkable albuminuria. Our data demonstrate that renal TECs take up FAs from blood (CD36-dependent) and primary urine (CD36-independent) and can store excess FAs as neutral lipids. The results further show that renal tubules have hitherto largely unappreciated mechanisms by which the excretion of FAs into the urine is avoided.
Signatures of EMT, immunosuppression and inflammation of primary and recurrent human cutaneous squamous cell carcinoma at single-cell resolution
Authors: Li Xin , Zhao Shuang , Bian Xiaohui , Zhang Lining , Lu Lixia , Pei Shiyao , Dong Liang , Shi Wensheng , Huang Lingjuan , Zhang Xiyuan , Chen Mingliang , Chen Xiang , Yin Mingzhu
Published: July 2022

The recurrence of cutaneous squamous cell carcinoma (cSCC) after surgery remains a key factor affecting cSCC outcomes, which is related to the reprogramming of the tumour microenvironment (TME). Herein, we utilized single-cell RNA sequencing (scRNA-seq) to examine the dynamic changes in epithelial cells, T cells, myeloid cells and fibroblasts between primary and recurrent cSCC. We uncovered the immunosuppressed microenvironment in recurrent cSCC, which exhibited a T-cell- excluded and SPP1+ TAM-enriched status. In recurrent cSCC, CD8+ T cells showed high exhaustion and low inflammatory features, while SPP1+ TAMs displayed global protumour characteristics, including decreased phagocytosis and inflammation as well as increased angiogenesis. Furthermore, we found that the subgroups of SPP1+ tumour- associated macrophages (TAMs) harboured distinct functions. SPP1+ CD209high TAMs showed obvious features of phagocytosis, while SPP1+ CD209low TAMs tended to have a high angiogenic ability. A subpopulation of tumour-specific keratinocytes (TSKs) showed significant epithelial–mesenchymal transition (EMT) features in recurrent cSCC, which might be due to their active communication with IL7R+ cancer-associated fibroblasts (CAFs). In addition, we found that MDK could provoke different cell–cell interactions in cSCCs with distinctive staging. In primary cSCC, MDK was highly expressed in fibroblasts and could promote their proliferation and block the migration of tumour cells, while in recurrent cSCC, the high expression of MDK in TSKs promotes their proliferation and metastasis. Overall, our study provides insights into the critical mechanisms of cSCC progression, which might facilitate the development of a powerful system for the prevention and treatment of cSCC recurrence.
The contraction-expansion behaviour in the demosponge Tethya wilhelma is diurnal and light-controlled
Authors: Flensburg Sarah B. , Garm Anders , Funch Peter
Published: July 2022

Sponges (phylum Porifera) are metazoans without muscles and nervous system. Still, they perform coordinated behaviours, such as whole body contrations. Previous studies have indicated diurnal variability in number of contractions, and in expression of circadian clock genes. Here we show that diurnal patterns are present in the contraction-expansion behaviour of the demosponge Tethya wilhelma using infrared videography and a simulated night/day-cycle including sunset and sunrise mimic. In addition, we show that this behaviour is at least strongly influenced by the ambient light intensity and therefore implicates light-sensing capabilities in this sponge species. This is backed by our finding that T. wilhelma consistently contracts at sunrise, and that this pattern disappears both when the sponge is kept in constant darkness and when in constant light.
ppGpp and RNA-Polymerase Backtracking Guide Antibiotic-Induced Mutable Gambler Cells
Authors: Zhai Yin , Minnick P.J. , Pribis John P. , Garcia-Villada Libertad , Hastings P.J. , Herman Christophe , Rosenberg Susan M.
Published: July 2022

Antibiotics can induce mutations that cause antibiotic resistance, triggered by stress responses. The identities of the stress-response activators reveal environmental cues that elicit mutagenesis, and are weak links in mutagenesis networks, inhibition of which could slow evolution of resistance during antibiotic therapies. Despite pivotal importance, few identities and fewer functions of stress responses in mutagenesis are clear. Here, we identify the stringent starvation response in fluoroquinolone-antibiotic ciprofloxacin (stress)-induced mutagenesis. We show its role in transient differentiation of a mutable “gambler” cell subpopulation. Stringent activity is induced by reactive oxygen and upregulates two small (s)RNAs that induce the general stress response, which allows mutagenic DNA-break repair. Surprisingly, RNA polymerase and response-activator nucleotide (p)ppGpp promote ciprofloxacin-induced DNA-damage signaling. We propose a model for their regulation of DNA-damage processing in transcribed regions. The data demonstrate a critical node in ciprofloxacin-induced mutagenesis, imply RNA-polymerase regulation of DNA-break repair, and identify promising targets for resistance-resisting drugs.
Eight Unexpected Selenoprotein Families in ABC transport, in Organometallic Biochemistry in Clostridium difficile and other anaerobes, and in Methylmercury Biosynthesis
Authors: Haft Daniel H. , Gwadz Marc
Published: July 2022

A novel protein family related to mercury resistance protein MerB, which cleaves Hg-C bonds of organomercurial compounds, is a newly recognized selenoprotein, typically seen truncated in sequence databases at CU (cysteine-selenocysteine) dipeptide sites fifty residues before the true C-terminus. Inspection shows this protein occurs in a nine-gene neighborhood conserved in more than fifty bacterial species, taxonomically diverse but exclusively anaerobic, including spirochetes, deltaproteobacteria, and Gram-positive spore-formers Clostridium difficile and C. botulinum. Three included families are novel selenoproteins in most instances, including two ABC transporter subunits, one a substrate-binding protein with another CU motif, the other a permease subunit with selenocysteine at the substrate-gating position. Phylogenetic profiling shows a strong pattern of co-occurrence with Stickland metabolism selenoproteins, but an even closer link to a group of 8Fe-9S cofactor-type double-cubane proteins. These 8Fe-9S enzymes vary in count and in genome location but frequently sit next to the nine-gene locus. We have named the locus SAO, because of the Selenocysteine-Assisted Organometallic (SAO) biochemistry implied by an uptake ABC transporter with apparent metal-binding selenocysteines, complementary metal efflux pump SaoE, the MerB-like cytosolic enzyme now called SaoL, and comparative genomics signatures suggesting energy metabolism rather than metal resistance. Hypothesizing cycles of formation and dismutation of organometallic compounds involved in fermentative metabolism, we examined methylmercury formation proteins, and discovered most HgcA proteins are selenoproteins as well, with a CU motif N-terminal to the previously predicted start. Seeking additional rare and overlooked selenoproteins, tricky because of their rarity, could help reveal more candidate cryptic biochemical processes.
Bioorthogonal in-cell Labeling and Profiling of N6-isopentenyladenosine (i6A) Modified RNA
Authors: Wang Sheng , Li Yuanyuan , Zhou Hongling , Wang Li , Gan Youfang , Zhang Shusheng , Zheng Ya Ying , Sheng Jia , Wang Rui
Published: July 2022

Chemical modifications in RNAs play critical roles in structural diversification and functional regulation of many vital biochemical processes. Several hydrophobic prenyl-modifications have been discovered in a variety of RNA species since the 1990s. Prenyl groups are the feedstocks of terpene and many other biological molecules and the processes of prenylation in different macromolecules have been widely studied. We present here a new chemical biology technique to identify and label i6A, a prenyl-modified RNA residue, based on the unique reactivity of the prenyl group. We also found that iodine-mediated cycloaddition reactions of the prenyl group occurs in a superfast manner, and converts i6A from a hydrogen-bond acceptor into a donor. Based on this reactivity, we developed an iodine-mediated oxidation and reverse transcription (IMORT) method to profile cellular i6A residues with a single-base resolution, allowing for the transcriptome-wide detection and analysis of various i6A-containing RNA species.