bluuebunny/crossref_metadata_2025 huggingface dataset:
An Epidemiologic Analysis of Vulvovaginal Candidiasis and Antifungal Susceptibilities
Authors: Hösükoğlu Fadile Gaye , Ekşi Fahriye , Erinmez Mehmet , Uğur Mete Gürol
Published: July 2022

Inflammation of the vagina and vulva caused by Candida is called vulvovaginal candidiasis (VVC). Risk factors for VVC include pregnancy, diabetes mellitus, frequent oral sexual intercourse, and the use of tight synthetic underwear and systemic antibiotics. Candida albicans, which belongs to the normal flora of the vagina, is the most common cause of VVC. However, an increase in VVC episodes caused by non-albicans Candida species, including Candida glabrata, Candida tropicalis, Candida krusei and Candida parapsilosis, has been reported. In this study, a total of 100 Candida isolates obtained from patients with vaginitis symptoms were evaluated. The susceptibility of the Candida strains to amphotericin B, itraconazole, fluconazole, ketoconazole, voriconazole and caspofungin was investigated using the reference broth microdilution method. Risk factors and demographic characteristics of the patients and the identified Candida species were also investigated. Among the 100 Candida strains isolated from vaginal samples, 47 (47%) were C. albicans, 43 (43%) C. glabrata, 5 (5%) C. kefyr, 2 (2%) C. krusei, 2 (2%) C. tropicalis and 1 (1%) was Candida guilliermondii. The incidences of Candida susceptibility to caspofungin, fluconazole, itraconazole, voriconazole, ketoconazole and amphotericin B were 75%, 35%, 27%, 80%, 97% and 100%, respectively. Also, there was a significant difference in antifungal susceptibility among patients belonging to certain risk groups, such as patients previously using antibiotics and recurrent cases. Prevalence of non-albicans Candida species and antifungal resistance, especially against azoles, are both increasing, and certain risk factors should be monitored strictly.
Update on pain management in acute pancreatitis
Authors: Pandanaboyana Sanjay , Huang Wei , Windsor John A. , Drewes Asbjørn Mohr
Published: July 2022

Purpose of review

This review discusses the analgesic options available from randomized controlled trials and recent systematic reviews. The evidence from other settings is considered and the evidence specific to acute pancreatitis emphasized. This highlights the options that are best supported by evidence but also the options that warrant further clinical trials.

Recent findings

Nonsteroidal anti-inflammatory drugs and paracetamol can provide adequate pain relief in patients with acute pancreatitis when compared with opioids. Epidural analgesia provides optimum pain relief in the first 24 h of onset of acute pancreatitis in addition to potential improvement in pancreatic perfusion. Several experimental analgesics and acupuncture have potential as opioid sparing strategies. Opioids are needed for patients with severe pain, to which adjuvant and experimental analgesics might be added.

Among the many options for pain management, the following principles should apply:
The spectrum of diabetes in acute and chronic pancreatitis
Authors: Olesen Søren S. , Toledo Frederico G.S. , Hart Phil A.
Published: July 2022

Purpose of review

To discuss the spectrum of diabetes related to acute and chronic pancreatitis (which are types of pancreatogenic diabetes) and its overlapping features with type 1 and type 2 diabetes.

Recent findings

Patients with diabetes related to acute and chronic pancreatitis present clinically within a spectrum of overlapping features with other forms of diabetes. In this spectrum, glucose metabolism alterations range from increased insulin resistance following acute pancreatitis (resembling type 2 diabetes) towards a permanent loss of beta-cell function and impaired insulin secretion in end-stage chronic pancreatitis. Overlapping features with type 1 diabetes (beta cell autoantibodies) and type 2 diabetes (obesity, dyslipidemia, and hereditary/genetic factors) contribute to the heterogeneity of this spectrum.

Pancreatogenic diabetes secondary to acute or chronic pancreatitis is a heterogeneous entity with a variable clinical presentation, including many cases that are misdiagnosed and treated as type 2 diabetes. This is problematic as pancreatogenic diabetes is associated with a poor prognosis and entails special considerations for management. Recent discoveries showing overlapping features with type 1 and type 2 diabetes along with an improved understanding of its pathophysiology are expected to improve the diagnosis and treatment of these and other forms of pancreatogenic diabetes.
Endoscopic methods for the detection and treatment of gastric cancer
Authors: Niknam Negar , Obanor Steven , Lee Linda A.
Published: July 2022

Purpose of review

The intent of this review is to describe new advances in endoscopic approaches to surveillance and management of gastric cancer.

Recent findings

There are new endoscopic techniques and approaches that have improved the detection of gastric cancer, including narrow band imaging, confocal laser endocytomicroscopy and magnetically controlled capsule endoscopy. This article highlights the role of endoscopic submucosal dissection in the treatment of focal and diffuse gastric dysplasia and early gastric cancer with a discussion of indications, complications and outcomes. We review several recent guidelines addressing the surveillance strategies for individuals at high-risk for developing gastric cancer, such as those with atrophic gastritis and intestinal metaplasia, how gastric dysplasia and early gastric cancer can be endoscopically managed, and recommended surveillance after endoscopic intervention.

Endoscopic approaches are evolving rapidly that will improve detection of dysplasia and early gastric cancer in high-risk individuals. Surveillance guidelines from various international societies reflect differences in local experience and prevalence of gastric cancer. Endoscopic submucosal dissection is now widely accepted as a first-line approach to early gastric cancers that can be resected en-bloc.
Clinical and translational markers of severity and prognosis in chronic pancreatitis
Authors: Sirtl Simon , Beyer Georg , Mayerle Julia
Published: July 2022

Purpose of review

The incidence of chronic pancreatitis as a progressive inflammation and fibrosis syndrome is on the rise due to increasing awareness and improved imaging modalities. Numerous classification systems have been suggested in recent years to describe the disease, but only few of them have been used to classify the severity and prognostic significance of the disease. Biomarkers for severity and (early) chronic pancreatitis diagnosis are not yet ready for clinical application.

Recent findings

In using the M-ANNHEIM and Chronic Pancreatitis Prognosis Score (COPPS) classification system, the severity assessment and short- and medium-term disease progression is available. A prospectively validated biomarker for early chronic pancreatitis diagnosis is not yet available, metabolome-based approaches seem to have the greatest potential for clinical translation.

Currently, due to the lack of universal definition for the early disease stage of chronic pancreatitis, it is difficult to accurately classify these patient cohorts in existing scoring systems. In principle, setting up a suitable scoring system would allow surveillance and establish a therapy approaches flanked by corresponding biomarker panel development. Therapy management of chronic pancreatitis and monitoring by means of scoring systems (such as the COPPS) would make a decisive contribution to improving patient treatment.
Type 3 autoimmune pancreatitis (immune checkpoint inhibitor-induced pancreatitis)
Authors: Sayed Ahmed Ahmed , Abreo Michael , Thomas Anusha , Chari Suresh T.
Published: July 2022

Purpose of review

Type 3 auto-immune pancreatitis (AIP) is a rare immune-related adverse event (irAE) because of immune checkpoint inhibitor (ICI) therapy employed in the management of advanced malignancies. The evaluation and management of this disease entity is not well documented in the literature. We summarize the available information on the clinical profile, diagnosis, and treatment of this disorder.

Recent findings

ICI-pancreatic injury (ICI-PI) is a form of AIP, recently termed type 3 AIP, which may present as an asymptomatic lipase elevation or clinical pancreatitis, that is, abdominal pain and elevated lipase. CT findings of pancreatitis may be absent in some cases. Diagnosis is based on a temporal relationship to ICI exposure and the absence of other cause of pancreatitis. Combination ICIs increase the risk of type 3 AIP compared with ICI monotherapy. Though corticosteroids are used for ICIP, their role and benefit remain unclear to date. Holding immunotherapy carries the risk of progression of underlying cancer.

ICI-PI is a unique form of AIP (type 3) with a distinct disease profile. The majority of patients with ICIPI are asymptomatic and steroid therapy has unclear benefits.
Urine Proteomics Reveals Sex-Specific Response to Total Pancreatectomy With Islet Autotransplantation
Authors: Bennike Tue Bjerg , Templeton Kate , Fujimura Kimino , Bellin Melena D. , Ahmed Saima , Schlaffner Christoph N. , Arora Rohit , Cruz-Monserrate Zobeida , Arnaout Ramy , Beilman Gregory J. , Grover Amit S. , Conwell Darwin L. , Steen Hanno
Published: July 2022

Objectives

Total pancreatectomy with islet autotransplantation (TPIAT) is a surgical option for refractory chronic pancreatitis-related pain. Despite the known clinical implications of TPIAT, the molecular effects remain poorly investigated. We performed the first hypothesis-generating study of the urinary proteome before and after TPIAT.

Methods

Twenty-two patients eligible for TPIAT were prospectively enrolled. Urine samples were collected the week before and 12 to 18 months after TPIAT. The urine samples were prepared for bottom-up label-free quantitative proteomics using the “MStern” protocol.

Results

Using 17 paired samples, we identified 2477 urinary proteins, of which 301 were significantly changed post-TPIAT versus pre-TPIAT. Our quantitative analysis revealed that the molecular response to TPIAT was highly sex-specific, with pronounced sex differences pre-TPIAT but minimal differences afterward. Comparing post-TPIAT versus pre-TPIAT, we found changes in cell-cell adhesion, intracellular vacuoles, and immune response proteins. After surgery, immunoglobulins, complement proteins, and cathepsins were increased, findings that may reflect glomerular damage. Finally, we identified both known and novel markers for immunoglobulin A nephropathy after 1 patient developed the disease 2 years after TPIAT.

Conclusions

We found distinct changes in the urinary proteomic profile after TPIAT and the response to TPIAT is highly sex-specific.
Preterm Infant Fecal Microbiota and Metabolite Profiles Are Modulated in a Probiotic Specific Manner
Authors: Larke Jules A. , Kuhn-Riordon Kara , Taft Diana H. , Sohn Kristin , Iqbal Sameeia , Underwood Mark A. , Mills David A. , Slupsky Carolyn M.
Published: July 2022

Objectives:

To compare the impact of two probiotic supplements on fecal microbiota and metabolites, as well as on gut inflammation in human milk-fed preterm infants.

Methods:

In this single-center observational cohort study, we assessed the effects of Bifidobacterium longum subsp. infantis or Lactobacillus reuteri supplementation on the infant gut microbiota by 16S rRNA gene sequencing and fecal metabolome by 1H nuclear magnetic resonance spectroscopy. Fecal calprotectin was measured as a marker of enteric inflammation. Aliquots of human or donor milk provided to each infant were also assessed to determine human milk oligosaccharide (HMO) content.

Results:

As expected, each probiotic treatment was associated with increased proportions of the respective bacterial taxon. Fecal HMOs were significantly higher in L. reuteri fed babies despite similar HMO content in the milk consumed. Fecal metabolites associated with bifidobacteria fermentation products were significantly increased in B. infantis supplemented infants. Fecal calprotectin was lower in infants receiving B. infantis relative to L. reuteri (P < 0.01, Wilcoxon rank-sum test) and was negatively associated with the microbial metabolite indole-3-lactate (ILA).

Conclusions:

This study demonstrates that supplementing an HMO-catabolizing Bifidobacterium probiotic results in increased microbial metabolism of milk oligosaccharides and reduced intestinal inflammation relative to a noncatabolizing Lactobacillus probiotic in human milk-fed preterm infants. In this context, Bifidobacterium may provide greater benefit in human milk-fed infants via activation of the microbiota-metabolite-immune axis.
Pediatric Gastric Mucosal Calcinosis
Authors: Ngai Derek , Wolf Matthias , Kelley Shannon , Goyal Aakash
Published: July 2022

Gastric mucosal calcinosis (GMC) is the deposition of calcium salts in gastric tissue. We report a case of GMC in a pediatric patient with a prior history of cholelithiasis and nephrolithiasis who presented with abdominal pain and vomiting. Laboratory evaluation did not show any abnormalities. Upper endoscopy revealed numerous gastric nodules; biopsies revealed calcium deposition in the superficial lamina propria. Recognizing GMC may aid with evaluation of a patient with vague gastrointestinal symptoms.
Trust Your Instinct—Lower Intestinal Bleeding Caused by Ehlers-Danlos-Syndrome
Authors: Melchior Ralph , Funke Rudolf , Wilken Bernd , Jenke Andreas
Published: July 2022

We report a 2.5-year-old boy who was presented with acute lower gastrointestinal bleeding. Emergency endoscopy showed two active mucosal bleeding sites that were successfully clipped. Initially, multiple intestinal angiodysplasias were considered, ruled out by a second control endoscopy. Here, multiple superficial lesions were observed that bled upon contact by the endoscope, suggestive of connective tissue disorder. However, the patient showed no clinical dysmorphias, only hypermobility of the toes but no other symptoms typical for such disorders. Gene testing for Ehlers-Danlos-syndrome (EDS) revealed a pathogenic mutation in the COL3A1 causing loss-of-function of type 3-collagen. Thus, diagnosis of EDS type IV was established. Overall, EDS is a rare cause for intestinal bleeding in children, even in children with no other clinical symptoms. This case is the earliest presentation of EDS type IV with intestinal complications.
Analysis of Factors Affecting Postoperative Drainage After Comprehensive Rhinoplasty
Authors: Wu Gaoyang , Sun Yiyu , Sheng Lingling , Dai Tingting , Jiang Zhaohua , Cao Weigang , Li Shengli
Published: July 2022

This study aimed to explore and analyze the factors influencing the drainage volume after comprehensive rhinoplasty. The clinical data of 102 patients who underwent comprehensive rhinoplasty at Shanghai Ninth People’s Hospital affiliated to Shanghai Jiao Tong University School of Medicine from August 2019 to August 2021 were retrospectively analyzed. The effects of age, sex, body mass index, whether an osteotomy was performed, and whether a nasal septum flap was obtained on the indwelling time of the drainage tube after the operation were analyzed by single factor analysis and multiple logistic regression analysis. Age, body mass index, whether it was a primary rhinoplasty, whether an osteotomy was performed, and whether a nasal septum flap was obtained were the influencing factors for drainage time after augmentation rhinoplasty (P<0.05). Sex had little effect on the drainage time after comprehensive rhinoplasty (P>0.05). Body mass index, whether an osteotomy was performed and whether a nasal septum flap was obtained were the independent influencing factors for the postoperative drainage time (P<0.05). For patients with multiple independent influencing factors, individualized management during the perioperative period should be promoted, and reasonable treatment strategies should be formulated, so as to reduce the indwelling time of the drainage tube after the operation.
Changes in Tears Monocyte Chemoattractant Protein-1 Level After External Dacryocystorhinostomy in Primary Acquired Nasolacrimal Duct Obstruction
Authors: Karabulut Müjdat , Saruhan Ercan
Published: July 2022

Background:

The authors aimed to define tears monocyte chemoattractant protein-1 (MCP-1) changes after external dacryocystorhinostomy surgery.

Materials and Methods:

Tears samples were collected with a Schirmer strip and stored in Eppendorf tubes at −80°C. At the end of the study, the papers were cut into small pieces and incubated with phosphate-buffered saline solution. Monocyte chemoattractant protein-1 levels were determined by using an enzyme-linked immunosorbent assays kit.

Results:

The MCP-1 levels were 498.66±101.35, 576.40±149.78, 422.53±85.94, and 436.96±81.38 ng/L before surgery, in the first week, the first, and third months after surgery, respectively. Its level significantly increased in the first week compared with the preoperative level (P<0.001). There was a prominent decrease in the postoperative first month (P<0.001). In the third postoperative month, the mean MCP-1 level was not significantly increased compared with the postoperative first month (P=0.196).

Conclusion:

The tears MCP-1 level was significantly decreased after external dacryocystorhinostomy surgery.
Analysis of Chinese Patients’ Satisfaction After Rhinoplasty With FACE-Q Rhinoplasty ModuleRhinoplasty With FACE-Q RM
Authors: Wang Xin , Wang Huan , You Jianjun , Zheng Ruobing , Xu Yihao , Fan Fei
Published: July 2022

Objective:

The literature on the patients’ satisfaction after rhinoplasty is limited. The purpose of our study was to use the patient-reported outcome measures to study the difference of satisfaction between men and women and between different ages before and after the operation and to explore the factors of postoperative satisfaction difference in Chinese people.

Method:

A total of 707 patients who underwent surgery at our institution were reviewed. Satisfaction was evaluated by the FACE-Q Rhinoplasty module (FACE-Q RM).

Results:

Follow-up data were 100% complete and the median follow-up time was 1 year.

Postoperatively, there was a significant difference in comparison with preoperative in nose and nostrils items (P<0.001). The satisfaction rate in men and women was 98.36% and 96.90%, respectively. Most men are dissatisfied with their bridges of the nose, and women are not satisfied with the tip. But after the operation, they all improved to a certain extent. Moreover, the rate of satisfaction in younger and older people was 96.80% and 100%, respectively. The younger people were more dissatisfied with the tip and size of the nostrils, whereas the older people were not satisfied with their bridges and well-matched nostrils. Univariate analysis showed that marital status was the factor, influencing satisfaction for nostrils (P=0.005).

Conclusion:

The FACE-Q RM scales are useful measures to assess patients’ satisfaction and confirm in what areas they are satisfied and most importantly, where they are not. We believe that the FACE-Q RM should be used before every patient.
Personalized 3D-printed Titanium Cutting Guide and Prefabricated Osteosynthesis Plate for Mandibular Step Osteotomy to Treat Severe Mandibular Prognathism
Authors: Kim Sang-Hun , Kim Ah-Hyeon , Choi Yoon Jeong , Jung Young-Soo , Kim Jun-Young
Published: July 2022

Mandibular step osteotomy, performed for mandibular prognathism, is a difficult and time-consuming procedure. Virtual computer surgery and computer-aided design & computer-aided manufacturing have demonstrated accurate results in orthognathic surgery, though not used for mandibular step osteotomy yet. In this study, the authors report the case of a 21-year-old man with severe mandibular prognathism, with a reverse overjet of 12 mm. Step osteotomy, a modified method of body osteotomy, was planned virtually and performed using 3-dimensional (3D) printed titanium surgical guides and osteosynthesis plates, using computer-aided design & computer-aided manufacturing. At the 6-month postoperative follow-up, there were no notable complications, and normal healing was observed. Each segment was stably in place with the prefabricated plates. The proximal segments were not sagged medially or laterally. With 3D-printed surgical guides and osteosynthesis plates, intraoperative complications, such as injury to adjacent teeth and nerves, could be avoided. They also showed reasonable accuracy and helped reduce operative time and improve outcomes. Unlike surgical guides made of resin/polyamide, titanium surgical guides can be made thinner, which can reduce the extent of detachment. They also did not undergo any deterioration during the operation. Cutting guides and prefabricated plates using virtual surgical planning and 3D printing have many advantages, including reduced preoperative preparation time and operative time, reduced incidence of intraoperative complications, and improved outcomes. However, limitations still exist and further studies are required.
Different Characteristics of Orbital Soft Tissue Expansion in Graves Orbitopathy: Extraocular Muscle Expansion is Correlated to Disease Activity While Fat Tissue Volume With Duration
Authors: Ma Lan , Hui Shiqi , Li Yang , Hou Zhijia , Liu Zhaohui , Chang Qinglin , Zhang Hanqiao , Li Dongmei
Published: July 2022

This study aimed to describe the correlation between some clinical features and orbital soft tissue volume in Graves orbitopathy (GO). The authors collected computed tomography scans from 56 untreated GO patients and measured fat volume (FV), intraorbital and extraorbital FV (IFV, EFV), bony cavity volume (BV), and extraocular muscle volume (MV) of the 112 orbits by using Mimics software. The ratio of soft tissue volume and BV were used to eliminate the individual variations. Outcomes were compared among groups and were correlated with clinical data, including age, sex, clinical activity score, duration, serum TSH receptor antibody (TRAb) level, body mass index and smoking status. Multivariate linear regression showed that higher MV/BV is associated with higher CAS and TRAb level (P<0.001, 0.005, respectively). No relationship was found between MV/BV and duration, sex, age, and body mass index. IFV/BV was related to duration (β=0.138, 95% confidence interval: 0.076–0.201, P<0.001), and did not correlate to clinical activity. IFV and MV are positively associated with exophthalmometry (P=0.009, <0.001, respectively), while orbital bony volume (BV) is negatively correlated with exophthalmometry (P=0.025). Results suggested TRAb level can impact the severity of GO mainly by affecting extraocular muscle rather than fat tissue. MV of GO is associated with disease activity, whereas IFV is correlated with duration and increases over time.
Complications and Treatments of Pseudomonas aeruginosa Infection After Rhinoplasty With Implants: A Clinical Study
Authors: Zeng Qi , Hu Yun-Gang , Tang Yu-Xi , Yu Bao-Fu , Li Xiao-Lin
Published: July 2022

Background:

Pseudomonas aeruginosa is an opportunistic pathogen, and because of its specificity, its treatments appear tricky in postrhinoplasty infections with internal implants. This study summarizes the clinical characteristics and treatment of this type of infections to provide some reference for clinical work.

Methods:

We retrospectively analyzed 10 patients who were diagnosed with a nasal infection of P. aeruginosa after implant nasal augmentation. The results of the bacterial culture and drug sensitivity test of the patients’ wound secretions were summarized and analyzed. We summarized the characteristics of the patients’ infection and the treatments, and we also summarized the patients’ prognosis.

Results:

In these 10 cases, their implants included rib cartilage and ear cartilage alone, as well as their own cartilage combined with expanded polytetrafluoroethylene and silicone. All patients developed wound infections within 1 month after rhinoplasty, with bacterial cultures of P. aeruginosa. Prolonged use of sensitive antibiotics, as well as wound dressing changes, failed to keep the infection well under control. Patients whose implant was removed and thoroughly debrided within 1 week of infection did not experience any serious complications. In patients who were infected for >1 week before surgery to remove the implants, complications such as nasal column necrosis and nasal contracture occurred, and later the nasal repair was performed after multiple surgeries.

Conclusions:

For bacterial infections in postrhinoplasty wounds with implants, we recommend early bacterial culture. If the infection is clearly P. aeruginosa, the implant should be removed and thoroughly debrided as soon as possible to avoid serious complications.

Level of Evidence:

Level IV.
Prevention and management of hospital-acquired pressure injury among patients with lung disease in a hospital: a best practice implementation project
Authors: Su Jui-Yuan , Mu Pei-Fan , Wang Ching-Hui , Chen Yu-Shang , Cheng Ting-Yin , Lee Mei-Yin
Published: July 2022

Objectives:

The aim of this project was to promote evidence-based practice in the prevention and management of pressure injury in lung disease patients.

Introduction:

Pressure injury is a crucial quality indicator for hospital care of patients. The pressure injury incidence threshold in the chest wards has been exceeding that of the general ward (0.128%), which may extend patients’ hospital stay.

Methods:

Clinical audits were performed using the Joanna Briggs Institute Practical Application of Clinical Evidence System and Getting Research into Practice (GRiP) audit and feedback tool. Twelve audit criteria representing best practice recommendations for preventing and managing pressure injury among lung disease patients were used. A baseline audit was performed to measure the degree of consistency between existing practice and best practice. This project used the GRiP analysis and multiple strategies to develop care protocols for pressure injury prevention and management. A follow-up audit was conducted to measure changes in clinical practice and pressure injury incidence.

Results:

Postimplementation audit compliance rates improved for the following criteria: skin assessment for identifying pressure injury indications (from 31 to 81%), identification of pressure injury risk score/category (from 19 to 88%), employment of nutritional assessment tools (from 8 to 93%), and provision of information regarding oral nutritional supplements (from 23 to 84%). Furthermore, patients learning the pressure injury care protocols (from 48 to 93%), the receipt of additional skin protection measures, and repositioning of vulnerable areas to relieve pressure increased to 100 and 93%, respectively. After project implementation, the monthly pressure injury incidence decreased markedly from 0.075 to 0.021%.

Conclusion:

The success factors of this project are attributable to leadership, open communication, multiple learning-by-doing strategies, regular audits, and the promotion of patient and family engagement.
Associations between general sleep quality and measures of functioning and cognition in subjects recently diagnosed with bipolar disorder
Authors: Montezano Bruno Braga , de A. Cardoso Taiane , de Mattos Souza Luciano D. , Moreira Fernanda Pedrotti , Mondin Thaíse Campos , da Silva Ricardo A. , Jansen Karen
Published: July 2022

The present study aims to assess the association between sleep quality and the functional and cognitive impairment in subjects that recently converted to bipolar disorder (BD), subjects with past major depressive disorder (MDD) and subjects with recurrent MDD. This was a cross-sectional study corresponding to a second wave of a cohort study with a community sample. The first wave included 585 subjects diagnosed with MDD. Mood episodes were assessed through structured clinical interview. Functional and objective cognitive impairments were measured by the Functional Assessment Short Test (FAST) and Letter-number sequencing from Wechsler Adult Intelligence Scale III, respectively, and Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA) was used for subjective cognition measure. Sleep quality was assessed by Pittsburgh Sleep Quality Index (PSQI). In PSQI, FAST and COBRA, we found significantly worse scores in the BD and recurrent MDD groups when compared to past MDD group. Our findings also showed a significant association between functioning and subjective cognition with general sleep quality in all observed groups. We reinforce the need to follow-up for maintenance of functional and cognitive impairment, notably with BD patients, who may suffer in addition to damage caused by sleep alterations, also with neuroprogression in the long term.
A widely distributed gene cluster compensates for uricase loss in hominids
Authors: Liu Yuanyuan , Jarman J. Bryce , Low Yen S. , Huang Steven , Chen Haoqing , DeFeo Mary E. , Sekiba Kazuma , Hou Bi-Huei , Ganesan Calyani , Pao Alan C. , Gombar Saurabh , Dodd Dylan
Published: July 2022

Approximately 15% of US adults have circulating levels of uric acid above its solubility limit, which is causally linked to the disease gout. In most mammals, uric acid elimination is facilitated by the enzyme uricase. However, human uricase is a pseudogene, having been inactivated early in hominid evolution. Though it has long been known that uric acid is eliminated in the gut, the role of the gut microbiota in hyperuricemia has not been studied. Here we identify a widely distributed bacterial gene cluster that encodes a pathway for uric acid degradation. Stable isotope tracing demonstrates that gut bacteria metabolize uric acid to xanthine or short chain fatty acids. Ablation of the microbiota in uricase-deficient mice causes severe hyperuricemia, and anaerobe-targeted antibiotics increase the risk of gout in humans. These data reveal a role for the gut microbiota in uric acid excretion and highlight the potential for microbiome-targeted therapeutics in hyperuricemia.
A Targeted Approach for Evaluating DUX4-Regulated Proteins as Potential Serum Biomarkers for Facioscapulohumeral Muscular Dystrophy Using Immunoassay Proteomics
Authors: Campbell Amy E. , Arjomand Jamshid , King Oliver D. , Tawil Rabi , Jagannathan Sujatha
Published: July 2022

Background

Facioscapulohumeral muscular dystrophy (FSHD) is a progressive myopathy caused by misexpression of the double homeobox 4 (DUX4) embryonic transcription factor in skeletal muscle. Identifying quantitative and minimally invasive FSHD biomarkers to report on DUX4 activity will significantly accelerate therapeutic development.

Objective

The goal of this study was to analyze secreted proteins already known to be induced by DUX4 in order to identify potential blood-based molecular FSHD biomarkers.

Methods

We used high-throughput, multiplex immunoassays from Olink Proteomics to measure the levels of several known DUX4-induced genes in a cellular myoblast model of FSHD, in FSHD patient-derived myotube cell cultures, and in serum from individuals with FSHD. Levels of other proteins on the Olink Proteomics panels containing these DUX4 targets were also examined in secondary exploratory analysis.

Results

Placental alkaline phosphatase (ALPP) levels correlated with DUX4 expression in both cell-based FSHD systems but did not distinguish FSHD patient serum from healthy controls.

Conclusions

ALPP, as measured with the Olink Proteomics platform, is not a promising FSHD serum biomarker candidate but could be utilized to evaluate DUX4 activity in discovery research efforts.
Beta-Thalassemia minor and SARS-CoV-2, prevalence, severity, morbidity and mortality: a systematic review study
Authors: Lansiaux Edouard , Drouin Emmanuel , Bolm Carsten
Published: July 2022

Background

Since the first year of the COVID-19 global pandemic, a hypothesis concerning the possible protection/immunity of beta-thalassemia carriers remains in abeyance.

Methods

Three databases (Pubmed Central, Scopus and Google Scholar) were screened and checked in order to extract all studies about incidence of confirmed COVID-19 cases OR mortality rate OR severity assessment OR ICU admission among patients with beta-thalassemia minor, were included in this analysis. The language was limited to English. Studies such as case reports, review studies, and studies that did not have complete data for calculating incidences were excluded.

Results and discussion

Three studies upon 2265 were selected. According to our systematic-review meta-analysis, beta-thalassemia carriers could be less COVID-19 affected than general population [IRR= 0.9250(0.5752;1.4877)], affected by COVID-19 with a worst severity [OR=1.5933(0.4884;5.1981)], less admissible into ICU [IRR=0.3620(0.0025;51.6821)] and more susceptible to die from COVID-19 or one of its consequences [IRR=1.8542(0.7819;4.3970)]. However, all of those results stay insignificant with a bad p-value (respectively 0.7479, 0.4400, 0.6881, 0.1610). Other large case-control or registry studies are needed to confirm these trends.
Monkey Pox Virus (MPXV): Phylogenomics, Host-Pathogen Interactome, and Mutational Cascade
Authors: kumar Roshan , Nagar Shekhar , Haider Shazia , Sood Utkarsh , Ponnusamy Kalaiarasan , Dhingra Gauri Garg , Anand Shailly , Dua Ankita , Singh Mona , Sengar Manisha , Singh Indrakant Kumar , Lal Rup
Published: July 2022

While the world is still managing to recover from Covid-19 pandemic, Monkeypox awaits to bring in another global outbreak as a challenge to the entire mankind. However, Covid-19 pandemic have taught us lessons to move fast in viral genomic research to implement prevention and treatment strategies. One of the important aspects in Monkeypox virus should be immediately taken up is to gather insights of its evolutionary lineage based on the genomic studies. We have thus analysed the genome sequences of reported isolates of Monkeypox in the present study through phylogenomics. Host-pathogen interactions, mutation prevalence and evolutionary dynamics of this virus were investigated for all the documented isolates. Phylogenetic exploration revealed the clustering of strain Israel 2018 (MN 648051.1) from Clade I with the four isolates reported from the recent outbreak. An in-depth scrutiny of the host-pathogen interactome identified protein E3, serine protease inhibitor-2 (SPI-2), protein K7, and cytokine response-modifying protein B (CrmB) as the major regulatory hubs. Among these, the CrmB protein (dN/dS ≈ 1.61) was detected to be operating through positive selection. It possibly attests a selective advantage with the monkeypox virus in protecting the infected cells from antiviral responses elicited by the host. Studies also revealed that CrmB protein exhibited several mutations, the majority of which were destabilizing (ΔΔG >0). While this study identified a large number of mutations within the newly outbreak clade, it also reflected that we need to move fast with the genomic analysis of the newly detected strains from around the world to develop better prevention and treatment methods
Tumor suppressor Hypermethylated in Cancer 1 represses expression of cell cycle regulator E2F7 in human primary cells
Authors: Lanikova Lucie , Svec Jiri , Janeckova Lucie , Pospichalova Vendula , Dibus Nikol , Vojtechova Martina , Hrckulak Dusan , Sloncova Eva , Strnad Hynek , Korinek Vladimir
Published: July 2022

Hypermethylated in Cancer 1 (HIC1) is an established tumor suppressor, which is frequently inactivated in various cancers. In colorectal carcinoma (CRC), silencing of HIC1 has been recognized as one of the important events in malignant tumor progression. Strikingly, CRC patients with high HIC1 expression have a worse prognosis than patients with relatively lowHIC1mRNA levels. To analyze the function of HIC1, we performed expression profiling of human primary fibroblasts after downregulation of HIC1 by RNA interference. We show that HIC1 deficiency triggers a p53-dependent response and that disruption of theHIC1gene in human colon cells delays cell cycle progression under serum deficiency conditions. Moreover, treatment with etoposide, a DNA-damaging agent, significantly impairs the proliferation rate and dynamics of damaged DNA repair in HIC1-deficient compared with wild-type cells. One of the genes upregulated in HIC1-depleted cells encodes cell cycle regulator E2F7. E2F7 is an atypical member of the E2F family, which functions primarily as a transcriptional repressor, and its downregulation is essential for proper cell cycle progression and expression of genes involved in DNA repair. We demonstrated that E2F7 is indeed the target of transcriptional repression mediated by HIC1. Moreover, our results suggest that the phenotypic manifestations associated with loss of theHIC1gene, in particular the changes in cell cycle progression and slowed repair of damaged DNA, are caused by dysregulation of E2F7 expression. Finally, we observed an inverse relationship between HIC1 and E2F7 in a panel of CRC. Importantly, CRC patients who express relatively high levels of E2F7 have a remarkably better prognosis than patients with intermediate or low levels of E2F7 expression.
Multivariate chemogenomic screening prioritizes new macrofilaricidal leads
Authors: Wheeler Nicolas J. , Ryan Kaetlyn T. , Gallo Kendra J. , Henthorn Clair R. , Ericksen Spencer S. , Chan John D. , Zamanian Mostafa
Published: July 2022

Development of direct acting macrofilaricides for the treatment of human filariases is hampered by limitations in screening throughput imposed by the parasite life cycle. Efforts to circumvent arduous screening of adult filariae include drug repurposing and high-throughput screens that target commensal bacteria.In vitroadult screens typically assess single phenotypes without prior enrichment for chemicals with antifilarial potential. We developed a multivariate screen that identified dozens of compounds with submicromolar macrofilaricidal activity, achieving a hit rate of >50% by leveraging abundantly accessible microfilariae. Adult assays were multiplexed to thoroughly characterize compound activity across relevant parasite fitness traits, including neuromuscular control, fecundity, metabolism, and viability. 17 compounds from a diverse chemogenomic library elicited strong effects on at least one adult trait, with differential potency against microfilariae and adults. Stage-specific drug effects may be crucial to limiting adverse events in endemic regions, and our screen identified five compounds with high potency against adults but low potency or slow-acting microfilaricidal effects, at least one of which acts through a novel mechanism. We show that the use of microfilariae in a primary screen outperforms model nematode developmental assays and virtual screening of protein structures inferred with deep-learning. These data provide new leads for drug development, and the high-content and multiplex assays set a new foundation for antifilarial discovery.
MINFLUX dissects the unimpeded walking of kinesin-1
Authors: Wolff Jan O. , Scheiderer Lukas , Engelhardt Tobias , Engelhardt Johann , Matthias Jessica , Hell Stefan W.
Published: July 2022

We report on an interferometric MINFLUX microscope that records protein movements with down to 1.7 nm precision within less than 1 ms. While such spatio-temporal resolution has so far required linking a strongly scattering 30-500 nm diameter bead to the much smaller protein, MINFLUX localization requires the detection of only down to 20 photons from an ~1-nm sized fluorophore. Harnessing this resolution, we dissect the unhindered stepping of the motor protein kinesin-1 on microtubules at up to physiological ATP concentrations. By attaching the fluorophore to different kinesin-1 sites and resolving steps and substeps of these protein constructs, we uncover a three-dimensional orientation change of the unbound kinesin head. We also find that kinesin-1 takes up ATP while only one head is bound, whereas hydrolysis of ATP occurs with both heads bound to the microtubule, resolving a long-standing conundrum of its mechanochemical cycle. Our results establish MINFLUX as a non-invasive tool for tracking protein movements and probing submillisecond structural rearrangements with nanometer resolution.
Unsupervised determination of lung tumor margin with widefield polarimetric second-harmonic generation microscopy
Authors: Mirsanaye Kamdin , Castaño Leonardo Uribe , Kamaliddin Yasmeen , Golaraei Ahmad , Kontenis Lukas , Žurauskas Edvardas , Navab Roya , Yasufuku Kazuhiro , Tsao Ming-Sound , Wilson Brian C. , Barzda Virginijus
Published: July 2022

The extracellular matrix (ECM) is amongst many tissue components affected by cancer, however, morphological changes of the ECM are not well-understood and thus, often omitted from diagnostic considerations. Polarimetric second-harmonic generation (P-SHG) microscopy allows for visualization and characterization of collagen ultrastructure in the ECM, aiding in better understanding of the changes induced by cancer throughout the tissue. In this paper, a large region of hematoxylin and eosin-stained human lung section, encompassing a tumor margin, connecting a significant tumor portion to normal tissue was imaged with P-SHG microscopy. The resulting polarimetric parameters were utilized in principal components analysis and unsupervised k-means clustering to separate normal- and tumor-like tissue. Consequently, a pseudo-color map of the clustered tissue regions is generated to highlight the irregularity of the ECM collagen structure throughout the region of interest and to identify the tumor margin.
Evaluating UV-C sensitivity ofCoxiella burnetiiin Skim Milk using a Bench-Scale Collimated Beam System and Comparative Study with High-Temperature Short-Time Pasteurization
Authors: Pendyala Brahmaiah , Vashisht Pranav , Chen Fur-Chi , Sanchez Savannah E. , Comstock Bob , Omsland Anders , Patras Ankit
Published: July 2022

Coxiella burnetiiis a zoonotic Gram-negative obligate intracellular bacterial pathogen and the causative agent of Query (Q) fever in humans. Contamination of milk byC. burnetiias a consequence of livestock infection is a significant public health concern. Effective methods to inactivateC. burnetiiin milk is a critical aspect of food safety. In this study, we measured optical light attenuation factors; absorption, scattering, and reflection of skim milk (SM) and considered for evaluation of delivered UV dose under stirred conditions. The accuracy of the method followed for the estimation of delivered UV dose in SM was verified by comparative studies ofEscherichia coliATCC 25922 inactivation in phosphate buffer (transparent fluid), and humic acid (opaque fluid). Absorption, scattering coefficient, and the reflectance of SM at 254 nm was measured as 19 ± 0.3/cm. 26 ± 0.5/cm and 10.6 %, respectively. SM inoculated withC. burnetiiwas irradiated using a collimated beam device equipped with a low-pressure UV-C254 nmlamp at doses from 0 – 12 mJ·cm-2. Results showed a log-linear inactivation ofC. burnetiiin SM with UV-C sensitivity (D10) value of 4.1 ± 0.04 mJ·cm-2. Similar inactivation kinetics was observed withSalmonella enterica serovarMuenchen ATCC BAA 1674 in SM and thereby suggested as a suitable surrogate toC. burnetiifor pilot scale UV-C processing studies of SM.
Strain dropouts reveal interactions that govern the metabolic output of the gut microbiome
Authors: Wang Min , Osborn Lucas J. , Jain Sunit , Meng Xiandong , Weakley Allison , Yan Jia , Massey William J. , Varadharajan Venkateshwari , Horak Anthony , Banerjee Rakhee , Allende Daniela S. , Chan Ricky E. , Hajjar Adeline M. , Dimas Alejandra , Zhao Aishan , Nagashima Kazuki , Cheng Alice G. , Higginbottom Steven , Brown J. Mark , Fischbach Michael A.
Published: July 2022

The gut microbiome is complex, raising questions about the role of individual strains in the community. Here, we address this question by focusing on a functional unit within the community, the metabolic niche that controls bile acid 7α-dehydroxylation. By constructing variants of a complex defined community in which we drop out strains that occupy this niche, we explore how interactions within and between niches shape community-level metabolism. Omitting both members of the niche,Clostridium scindens(Cs) andClostridium hylemonae(Ch), eliminates secondary bile acid production and reshapes the community in a highly specific manner: eight strains go up or down in relative abundance by >100-fold, while the remaining strains are largely unaffected. In single-strain dropout communities (i.e., a strain swap within the niche),CsandChreach the same relative abundance and dehydroxylate bile acids to a similar extent. However, the effect on strains in other niches differs markedly:Clostridium sporogenesincreases >1000-fold in the ΔCsbut not ΔChdropout, reshaping the pool of microbiome-derived phenylalanine metabolites. Thus, strains that are functionally redundant within a niche can have widely varying impacts outside the niche, and a strain swap can ripple through the community in an unpredictable manner, resulting in a large impact on an unrelated community-level phenotype. Mice colonized by the ΔCsΔChcommunity show decreased liver steatosis relative to those colonized by the ΔChcommunity, demonstrating that a single strain from the microbiome can have a substantive impact on host physiology. Our work opens the door to the mechanistic studies of the role of an individual strain on community ecology and host physiology.
Multi-Molecular Hyperspectral PRM-SRS Imaging
Authors: Zhang Wenxu , Li Yajuan , Fung Anthony A. , Li Zhi , Jang Hongje , Zha Honghao , Chen Xiaoping , Gao Fangyuan , Wu Jane Y. , Sheng Huaxin , Yao Junjie , Skowronska-Krawczyk Dorota , Jain Sanjay , Shi Lingyan
Published: July 2022

Lipids play crucial roles in many biological processes under physiological and pathological conditions. Mapping spatial distribution and examining metabolic dynamics of different lipids in cells and tissues in situ are critical for understanding aging and diseases. Commonly used imaging methods, including mass spectrometry-based technologies or labeled imaging techniques, tend to disrupt the native environment of cells/tissues and have limited spatial or spectral resolution, while traditional optical imaging techniques still lack the capacity to distinguish chemical differences between lipid subtypes. To overcome these limitations, we developed a new hyperspectral imaging platform that integrates a Penalized Reference Matching algorithm with Stimulated Raman Scattering (PRM-SRS) microscopy. With this new approach, we directly visualized and identified multiple lipid species in cells and tissues in situ with high chemical specificity and subcellular resolution. High density lipoprotein (HDL) particles containing non-esterified cholesterol was observed in the kidney, indicating that these pools of cholesterol are ectopic deposits, or have yet to be enriched. We detected a higher Cholesterol to phosphatidylethanolamine (PE) ratio inside the granule cells of hippocampal samples in old mice, suggesting altered membrane lipid synthesis and metabolism in aging brains. PRM-SRS imaging also revealed subcellular distributions of sphingosine and cardiolipin in the human brain sample. Compared with other techniques, PRM-SRS demonstrates unique advantages, including faster data processing and direct user-defined visualization with enhanced chemical specificity for distinguishing clinically relevant lipid subtypes in different organs and species. Our method has broad applications in multiplexed cell and tissue imaging.