bluuebunny/crossref_metadata_2025 huggingface dataset:
What is the current status of childhood obesity in Saudi Arabia?: Evidence from 20,000 cases in the Eastern Province: A cross-sectional study
Authors: Albaker Waleed , Saklawi Rim , Bah Sulaiman , Motawei Kamaluddin , Futa Basem , Al-Hariri Mohammed
Published: July 2022

The prevalence rate of those overweight, as well as obesity among children in Saudi Arabia, keeps rising. The aim of the study was to estimate childhood obesity in the Eastern Province, Saudi Arabia.

Over the period 2016 to 2017, a cross-sectional campaign was carried out in the Eastern Province of Saudi Arabia. Data were collected from over 20,000 boys’ and girls’ schools. The campaign collected data on birthday/age, weight, height, sex, district in which the school is located, level of education, and blood pressure level.

The findings from the present study indicated a prevalence of 25.7% for overweight and obesity among high school-age students. More importantly, ≈35% of the study’s students have either elevated blood pressure or hypertension. The significant predictors of childhood obesity were education level, age, glucose level, and blood pressure.

The children in higher school levels originally from the Eastern Province had a high prevalence of overweight and obesity. Recommendations are made on the need of regular screening program among school-age children, as well as to continue raising awareness about childhood obesity.
Identification of molecular mechanisms underlying the therapeutic effects of Xintong granule in coronary artery disease by a network pharmacology and molecular docking approach
Authors: Huang Zhihong , Guo Siyu , Fu Changgeng , Zhou Wei , Stalin Antony , Zhang Jingyuan , Liu Xinkui , Jia Shanshan , Wu Chao , Lu Shan , Li Bingbing , Wu Zhishan , Tan Yingying , Fan Xiaotian , Cheng Guoliang , Mou Yanfang , Wu Jiarui
Published: July 2022

Coronary artery disease (CAD) is a cardiovascular disease characterized by atherosclerosis, angiogenesis, thrombogenesis, inflammation, etc. Xintong granule (XTG) is considered a practical therapeutic strategy in China for CAD. Although its therapeutic role in CAD has been reported, the molecular mechanisms of XTG in CAD have not yet been explored.

A network pharmacology approach including drug-likeness (DL) evaluation, oral bioavailability (OB) prediction, protein-protein interaction (PPI) network construction and analysis, and Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses was used to predict the active ingredients, potential targets, and molecular mechanisms of XTG associated with the treatment of CAD. Molecular docking analysis was performed to investigate the interactions between the active compounds and the underlying targets.

Fifty-one active ingredients of XTG and 294 CAD-related targets were screened for analysis. Gene Ontology enrichment analysis showed that the therapeutic targets of XTG in CAD are mainly involved in blood circulation and vascular regulation. KEGG pathway analysis indicated that XTG intervenes in CAD mainly through the regulation of fluid shear stress and atherosclerosis, the AGE-RAGE signaling pathway in diabetic complications, and the relaxin signaling pathway. Molecular docking analysis showed that each key active ingredient (quercetin, luteolin, kaempferol, stigmasterol, resveratrol, fisetin, gamma-sitosterol, and beta-sitosterol) of XTG can bind to the core targets of CAD (AKT1, JUN, RELA, MAPK8, NFKB1, EDN1, and NOS3).

The present study revealed the CAD treatment-related active ingredients, underlying targets, and potential molecular mechanisms of XTG acting by regulating fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, and relaxin signaling pathway.
Abdominal cocoon syndrome: Rare cause of intestinal obstruction—Case report and systematic review of literature
Authors: Chorti Angeliki , Panidis Stavros , Konstantinidis Dimitrios , Cheva Angeliki , Papavramidis Theodossis , Michalopoulos Antonios , Paramythiotis Daniel
Published: July 2022

Background:

Abdominal cocoon or sclerosing encapsulating peritonitis is an uncommon condition in which the small bowel is completely or partially encased by a thick fibrotic membrane. Our study presents a case of sclerosing encapsulating peritonitis and conducts a literature review.

Methods:

A bibliographic research was conducted. Our research comprised 97 articles. Gender, age, symptoms, diagnostic procedures, and treatment were all included in the database of patient characteristics.

Case presentation:

A 51-year-old man complaining of a 2-day history of minor diffuse abdominal pain, loss of appetite, and constipation was presented in emergency department. Physical examination was indicative of intestinal obstruction. Laboratory tests were normal. Diffuse intraperitoneal fluid and dilated small intestinal loops were discovered on computed tomography (CT). An exploratory laparotomy was recommended, in which the sac membrane was removed and adhesiolysis was performed. He was discharged on the tenth postoperative day.

Results:

There were 240 cases of abdominal cocoon syndrome in total. In terms of gender, 151 of 240 (62.9%) were male and 89 of 240 (37%) were female. Ages between 20 and 40 are most affected. Symptoms include abdominal pain and obstruction signs. For the diagnosis of abdominal cocoon syndrome, CT may be the gold standard imaging method. The surgical operation was the treatment of choice in the vast majority of cases (96.7%). Only 69 of 239 patients (28.9%) were detected prior to surgery, and CT was applied in these cases.

Conclusion:

Abdominal cocoon is a rare condition marked by recurrent episodes of intestinal obstruction. Surgical therapy is the most effective treatment option.
High-quality nursing care on psychological disorder in ovarian cancer during perioperative period: A systematic review and meta-analysis
Authors: Jin Peng , Sun Li-Li , Li Bin-Xin , Li Mei , Tian Wei
Published: July 2022

Background:

This study aimed to explore the effect of high-quality nursing care (HQNC) on psychological disorder in patients with ovarian cancer (OC) during the perioperative period (PPP).

Methods:

A literature search was performed at the Cochrane Library, PUBMED, Excerpt Medica Database, China National Knowledge Infrastructure, and Chinese Biomedical Literature Database from their inception until March 1, 2022. Two authors independently performed study selection, data collection, and methodological quality evaluation. The outcomes were anxiety (as measured by the Self-rating Anxiety Scale), depression (as measured by Self-rating Depression Scale), length of hospital stay, and rate of patient satisfaction.

Results:

Eight trials involving 742 patients with OC were included in this study. Results of the data analysis showed that patients who received HQNC had a more promising effect on anxiety relief (mean difference, −9.00; random 95% confidence interval, −11.36 to −6.63; P < .001) and depression decrease (mean difference, −7.62; random 95% confidence intervals, −8.45 to −6.78; P < .001) than patients who underwent routine nursing care.

Conclusion:

This study summarized the latest evidence of HQNC on psychological disorder relief in patients with OC during perioperative period. These findings showed that HQNC may benefit patients with anxiety and depression.
Age-specific influences of refractive error and illuminance on pupil diameter
Authors: Lee Yong-Sik , Kim Hui-June , Lim Dong-Kyu , Kim Myoung-Hee , Lee Koon-Ja
Published: July 2022

To assess the most influential factor for pupil diameter changes among age, illuminance, and refractive state and reestablish the optimal procedures for clinical applications based on refractive state and illuminance for different age groups.

The study was an observational study (repeated measure study). Participants included 219 Korean adults aged 20 to 69 years. Pupil diameters were measured using a pupilometer under scotopic, mesopic-low, and mesopic-high lighting conditions. Factor interactions among age, illuminance, and refractive state were evaluated using mixed linear model and chi-square automated interaction detection.

Illuminance mainly contributed to variations in pupil diameter of participants over 50 years, whereas the refractive state was the dominant controlling factor for the pupil variation in participants below 50 years. For more generalized application, the pupil diameter decreased with older age and brighter illuminance (P < .001, inverse correlation, all comparisons). The mean pupil diameter was significantly higher in myopes and emmetropes than in hyperopes (P < .001). Pupil diameter variation modeled using the mixed model confirmed age, illuminance, and refractive error as significant factors (P < .001).

Accounting for the interactions among age, illuminance, and refractive error and establishing their hierarchical dominance can be generalized using the chi-square automated interaction detection method and mixed model. Promoting age-dependent consideration for both illuminance and refractive state is necessary when pupil diameters play significant roles in clinical and manufacturing circumstances.
Histological changes and neural elements in the subacromial bursa on patients with rotator cuff tear: Pilot study
Authors: Choi Chang-Hyuk , Kwon Dae Gil , Oh Hoon-Kyu , Kim Jun Young , Kwon Dong Rak
Published: July 2022

Objective:

This study aimed to investigate the neural elements of the subacromial bursa (SAB) in rotator cuff tears.

Materials and methods:

Twenty patients with rotator cuff tears were recruited, and their visual analog scale (VAS) score, duration of symptoms, and range of motion (ROM), including flexion, external rotation, and internal rotation were evaluated. Tear size was measured using magnetic resonance imaging (MRI). The SAB specimens obtained during arthroscopic rotator cuff repair were studied using routine hematoxylin and eosin staining and immunohistochemistry (S-100 protein and PGP 9.5 protein). The SAB specimen for the control group was obtained from 2 fresh cadavers and 2 patients with acute humeral shaft fracture. The Mann-Whitney U test was applied to assess the difference between histological findings of the rotator cuff tear group and control group. The correlation between the histological findings and clinical features was evaluated using the Spearman correlation coefficient.

Results:

The mean duration of symptom was 10.2 ± 6.4 months. The preoperative average VAS score was 2.9 ± 1.2. The degrees of preoperative ROM in forward flexion and external and internal rotations were 143.8 ± 19.5, 49.5 ± 23.1, and –4.3 ± 4.2, respectively. The tear was 2.0 ± 0.9 cm. For histological findings, the number of neural elements per low power field in the rotator cuff tear group was significantly less than the control group in both immunohistochemical stainings (S-100: 0.5 ± 0.7 vs 2.8 ± 0.5, p < .01; PGP 9.5: 0.4 ± 0.7 vs 3.5 ± 0.6, p < .01). During the correlation analysis, the number of neural elements in the PGP 9.5 staining was negatively correlated with the ROM in forward flexion and external rotation.

Conclusion:

This study revealed that chronic rotator cuff tears may induce degeneration of neural elements in SAB.
Glasgow prognostic score predicts survival in patients with unresectable hepatocellular carcinoma treated with lenvatinib: a multicenter analysis
Authors: Tada Toshifumi , Kumada Takashi , Hiraoka Atsushi , Hirooka Masashi , Kariyama Kazuya , Tani Joji , Atsukawa Masanori , Takaguchi Koichi , Itobayashi Ei , Fukunishi Shinya , Tsuji Kunihiko , Ishikawa Toru , Tajiri Kazuto , Ochi Hironori , Yasuda Satoshi , Toyoda Hidenori , Hatanaka Takeshi , Kakizaki Satoru , Shimada Noritomo , Kawata Kazuhito , Tanaka Takaaki , Ohama Hideko , Nouso Kazuhiro , Morishita Asahiro , Tsutsui Akemi , Nagano Takuya , Itokawa Norio , Okubo Tomomi , Arai Taeang , Imai Michitaka , Naganuma Atsushi , Aoki Tomoko , Koizumi Yohei , Nakamura Shinichiro , Joko Kouji , Hiasa Yoichi , Kudo Masatoshi ,   On behalf of the Real-life Practice Experts for HCC (RELPEC) Study Group and the Hepatocellular Carcinoma Experts from 48 Clinics in Japan (HCC 48) Group
Published: July 2022

Objective

The use of Glasgow prognostic score (GPS), calculated using the serum C-reactive protein and albumin levels, to predict the outcomes of patients with unresectable hepatocellular carcinoma (HCC) treated with lenvatinib was investigated in this study.

Methods

A total of 508 patients with Child-Pugh class A HCC treated with lenvatinib were included in this study.

Results

The median overall and progression-free survivals were 20.4 months [95% confidence interval (CI), 17.7–23.2 months] and 7.5 months (95% CI, 6.8–8.5 months), respectively. The median overall survivals of patients with a GPS of 0, 1, and 2 were 28.5, 16.0, and 9.1 months, respectively (P < 0.001). When adjusted for age, sex, performance status, etiology, α-fetoprotein, macroscopic vascular invasion, extrahepatic spread, history of sorafenib therapy, and GPS, a GPS of 1 [hazard ratio (HR), 1.664; 95% CI, 1.258–2.201; P < 0.001] and a GPS of 2 (HR, 2.664; 95% CI, 1.861–3.813; P < 0.001) were found to be independently associated with overall survival. The median progression-free survivals of patients with a GPS of 0, 1, and 2 were 8.8, 6.8, and 3.8 months, respectively (P < 0.001). When adjusted for the same factors of overall survival, a GPS of 2 (HR, 2.010; 95% CI, 1.452–2.784; P < 0.001) was found to be independently associated with progression-free survival. As the albumin–bilirubin with tumor node metastasis score increased, the proportion of patients with a GPS of 1 or 2 increased (P < 0.001).

Conclusions

GPS can be used to predict survival in patients with unresectable HCC who were treated with lenvatinib.
External validation and comparison of simple tools to screen for nonalcoholic fatty liver disease in Chinese community population
Authors: Zhang Liuxin , Zhang Mengting , Wang Min , Wang Minxian , Zhang Ru , Wang Hongliang , Zhang Wei , Ding Yajie , Wang Jie
Published: July 2022

Background

Various noninvasive tools based on anthropometric indicators, blood lipids, and liver enzymes, etc. have been developed to screen for nonalcoholic fatty liver disease (NAFLD), with different diagnostic performance and cutoff values among studies. We aimed to validate and compare eight NAFLD-related models developed by simple indicators and to define their cutoff values in Chinese community population.

Methods

A cross-sectional study was conducted in a health examination cohort of 3259 people. NAFLD was diagnosed by ultrasonography. General, anthropometric and biochemical data were collected. Fatty liver index (FLI), fatty liver disease index (FLD), Zhejiang University index (ZJU), lipid accumulation product (LAP), regression formula of controlled attenuation parameter (CAP), waist-to-height ratio (WHtR), triglyceride and glucose index (TyG), and visceral adiposity index (VAI) were calculated. The accuracy and cutoff points to detect NAFLD were evaluated by area under the receiver operator characteristic curve and the maximum Youden index analysis, respectively. A head-to-head comparison between these models and Decision Curve Analysis (DCA) was conducted.

Results

In eight noninvasive diagnostic models of NAFLD, AUCs of FLI and FLD for NAFLD were higher than those of other models in the whole (0.852 and 0.852), male (0.826 and 0.824), and female (0.897 and 0.888) population, respectively. DCA showed that FLI, FLD, and ZJU have higher net benefit to screen for NAFLD compared to other models.

Conclusions

FLI and FLD could be the most accurate and applicable of eight models for the noninvasive diagnosis of NAFLD in both male and female groups.
Offspring from oocytes grown in frozen-thawed ovarian tissues transplanted to male and female bodies
Authors: Yan Jie , Cai Yu-Fang , Dai Shan-Jun , He Xiao-Jin , Sun Ying-Pu , Cao Yun-Xia , Qiao Jie , Chian Ri-Cheng
Published: July 2022

Objective:

There are few reports of live births from heterotopic transplantation of frozen-thawed ovarian tissue. The purpose of this study is to assess the follicular development in the frozen-thawed ovarian tissues following heterotopic transplantation in both female and male bodies.

Methods:

Cluster of differentiation 1 (CD1) mice (6-8 weeks) were used in this study as ovarian tissue donors and foster mothers for embryo transfer. Sperm from CD1 male mice were used for insemination by intracytoplasmic sperm injection (ICSI). Nude severe combined immunodeficiency mice (8 weeks) were employed as recipients of ovarian tissue transplantation. The frozen-thawed ovarian tissues were transplanted to 4 sites on each mouse, female and male, subcutaneously. After 3 months, both female and male mice were injected with 5.0 IU gonadotropins intraperitoneally. Post 48 hours of injection, the mouse was killed for ovarian transplant collection. Only fully grown oocytes with contacted cumulus cells (cumulus-oocyte complexes) were then selected for maturation in vitro. In vitro matured oocytes were inseminated with fresh sperm by ICSI, and the developed blastocysts were frozen using the vitrification method and stored until embryo transfer. After thawing, the thawed blastocysts were incubated for at least 2 hours before the transfer. The foster mice mothers mated with vasectomised male 3 days previously. Live birth was monitored at 19 days after transfer, and the resulted offspring was raised for fertility test.

Results:

The relatively high recovery rates of the transplanted ovarian tissues were collected in both frozen-thawed and fresh ovarian tissue transplants from both female and male bodies. The fully grown immature oocytes became mature in vitro and the fertilized zygotes developed to blastocyst stage. There are no differences between frozen-thawed and fresh ovarian transplants in term of oocyte quality and embryo development to blastocyst rates. Nineteen-day post-transfer, 3 foster mothers from the frozen-thawed ovarian tissue transplant group delivered 13 pups and the 4 foster mothers of the fresh ovarian tissue transplant group delivered 12 live pups. The produced offspring were normal in appearance and grew healthy and fertile.

Conclusions:

Our results attest that the follicles can survive and develop in the frozen-thawed ovarian tissues following the subcutaneous transplant to adult male mouse's body regardless of basal endocrinal environment. Those fully grown oocytes can produce healthy and fertile offspring which will provide the possibility for further mechanistic understanding of endocrinology of folliculogenesis.
Chinese expert consensus on clinical practice of female fertility preservation
Authors: Li Wen , Chian Ri-Cheng ,   on behalf of the Fertility Preservation Committee of Chinese Maternal and Child Association
Published: July 2022

Many female fertility preservation-related technologies have recently been developed in response to increasing demand for such treatments. To establish standard practices of female fertility preservation in China, the Chinese Maternal and Child Health Association Affiliated Fertility Preservation Professional Committee assembled specialists to construct a consensus, referring to the current clinical guidelines of some countries combined with clinical practice and expert opinions. The consensus includes two parts: (1) indications for female fertility preservation and related techniques, in which we sought to be inclusive regarding the indications for fertility preservation; and (2) practical guidance for the clinical application of the female fertility preservation technologies.
Gastroschisis at the León University Hospital, Nicaragua
Authors: Bucardo Dania María Pastora , Ramírez Paula Andrea Pimienta
Published: July 2022

Objective:

The prevalence of midline birth defects, such as gastroschisis, has increased worldwide, over the last few decades. This study aims to explore the prevalence, maternal epidemiological characteristics, and natural history of neonates affected by gastroschisis at the University Hospital of León city, Nicaragua.

Methods:

Data were collected from the birth defect surveillance system of the Hospital Oscar Danilo Rosales (HEODRA). The analysis included all pregnancies that had gastroschisis complications between January 1 and December 31, 2020. The prevalence of gastroschisis was calculated according to maternal age. The mothers were interviewed, and the clinical records of the newborns were reviewed.

Results:

Among the 4,460 deliveries included in this study, four cases of gastroschisis were identified, including three live births and one stillbirth. The gastroschisis rate was 8.9 per 10,000 live births (95% confidence interval [CI]: 0.18–17.8). The prevalence among mothers younger than 20 years and those older than 20 years was 26.4 (95% CI: –3.43 to 56.25) and 3.01 (95% CI: 2.89–8.90)/10,000 births, respectively. Mothers of gastroschisis-affected fetuses were of rural origin (n = 3), had normal body mass indexes (n = 3), were exposed to tobacco and wood smoke (n = 2), and one was exposed to pesticides during the periconceptional period. Primary closure of the gastroschisis was performed on one patient, and complex gastroschisis for intestinal perforation was observed in another patient. The mean hospitalization duration was 33 days, and two patients were discharged alive.

Conclusions:

Gastroschisis was a significant birth defect among children delivered at HEODRA in 2020. Its prevalence in Nicaragua was higher than that in other countries in the region. All complicated pregnancies were young women with unplanned pregnancies, from rural areas, with exposure to secondhand smoke, and without vitamin supplements before or during the first trimester of pregnancy. Only 67% of infants survived after hospital discharge.
Microcephaly prevalence after the 2015 to 2016 Zika outbreak in Tangará da Serra, Brazil: a population-based study
Authors: da Silva Juliana Herrero , Terças-Trettel Ana Claudia Pereira , Boquett Juliano André , Franca Giovanny Vinicius Araujo , Cardoso-dos-Santos Augusto Cesar , Atanaka Marina , Oliveira Marcelo Zagonel , Terra Anna Pires , Vivi Viviane Karoline , de Oliveira Lucia Andreia Nunes , Schaedler Lucia , Alves Ronaldo Fernandes Santos , Schuler-Faccini Lavinia
Published: July 2022

Objective:

Prenatal infection with the Zika virus (ZIKV) can lead to congenital Zika syndrome (CZS), characterized by microcephaly and brain injury. However, there are questions regarding the prevalence of microcephaly/CZS after the ZIKV outbreak in defined geographic areas. This study aimed to identify adverse outcomes in live births of fetuses exposed in utero to the ZIKV, compared to unexposed births, as well as maternal sociodemographic, delivery, and birth characteristics.

Methods:

Here, we conducted a cross-sectional observational study to investigate the characteristics of all live births in the city of Tangará da Serra, Mato Grosso, Brazil, in 2016, after the outbreak of ZIKV infection in late 2015. All live births of children to women residing in the municipality of Tangará da Serra between January 1 and December 31, 2016, were evaluated, and head circumference was measured at birth and after 24 hours. Children born with microcephaly or a maternal history of confirmed or suspected prenatal ZIKV infection were evaluated by a multidisciplinary team. The outcomes of the exposed and non-exposed children were compared. Prevalence ratios and their respective 95% confidence intervals were calculated for sociodemographic, delivery, and live birth characteristics.

Results:

Of 1,441 live births, 106 (7.3%) were from mothers with confirmed or highly probable exposure to ZIKV. The prevalence of severe congenital microcephaly (41.7/10,000) in Tangará da Serra in 2016 was ten-fold higher than that in Latin America before 2015.

Conclusion:

This study may serve as a model to investigate possible outbreaks of infections in a defined geographical space in the future.
Liquiritin ameliorates metabolic and endocrine alterations in a mouse model of polycystic ovary syndrome
Authors: Li Zhi , Liu Yan , Liu Hai-Ou , Wu Zhi-Yong , Xu Cong-Jian , Zhang Fei-Fei
Published: July 2022

Objective:

Altered bile acid transformation induces low-grade chronic inflammation and may play an important role in the pathophysiology of polycystic ovary syndrome (PCOS). Liquiritincan regulate bile acid metabolism and anti-inflammatory properties; however, limited information is available regarding its therapeutic potential in PCOS.

Methods:

Female C57BL/6 mice were randomly assigned into four groups (n = 6 mice/group): the control, letrozole or dehydroepiandrosterone-induced PCOS groups, PCOS + 20 mg/kg liquiritin group, and control + liquiritin groups. After 21 days of treatment, the mice were euthanized, and the associated metabolism indications were investigated. Ovarian histological examinations were performed, and serum hormone concentration was measured. The expression of key genes involved in steroid hormone synthesis, ovarian follicle development, and ovulation was assessed.

Results:

Liquiritin reduced fasting blood glucose levels and increased insulin sensitivity compared to the PCOS group. Liquiritin also significantly decreased serum levels of total testosterone (P < 0.001) and dehydroepiandrosterone sulfate (P < 0.05) in the PCOS group. Histomorphological inspection of ovaries from the liquiritin group revealed fewer cystic dilated follicles than in the PCOS group. Moreover, liquiritinsignificantly (P < 0.01) decreased Cyp17a1, Cyp19a1, Fshr, Hsd3b2, Runx2, and Ccn2 mRNA expression compared to letrozole-induced PCOS.

Conclusion:

Liquiritin may be safe and helpful in ameliorating PCOS-associated hyperandrogenemia and hyperglycemia. However, clinical trials investigating different liquiritin dosages are needed to confirm these findings.
Susceptibilities of pus cultures in diabetic foot patients: an observational study
Authors: Asghar Muhammad Sohaib , Parkash Om , Sagar  , Singh Manjeet , Kumar Sumeet , Kumar Karan , Mehdi Asad , Khan Farmanullah , Chughtai Najeebullah , Ahmed Nisar
Published: July 2022

Objectives:

The aim of our study is to evaluate the organisms growing into the pus cultures of diabetic foot patients and to further document their sensitivity and resistance toward antibiotics.

Methods:

This study was conducted among admitted patients in the department of Medicine and Orthopedics, of a tertiary care hospital, including patients with known diabetes mellitus for the last 5 years, with a foot ulcer of any grade and a positive culture for bacterial growth. Cultures showing fungal growth were excluded.

Results:

There were 139 participants in our study with a mean age of 55.27 years, and mean HbA1c levels of 9.51%, 101 (72.66%) patients were males and 38 (27.33%) females. According to the Wagner classification; there were 48 (34.53%) patients in grade 2, 27 (19.42%) patients in grade 3, 54 (38.84%) patients in grade 4, and 10 (7.19%) patients in grade 5. The most frequently isolated bacteria were Staphylococcus aureus (43.16%), methicillin-resistant staphylococcal aureus (5.03%), Enterococcus species (5.75%), Streptococcus species (7.91%), Pseudomonas aeruginosa (20.14%), Escherichia coli (24.46%), Klebsiella pneumonia 7 (5.03%), Proteus vulgaris 6 (4.31%), Proteus mirabilis 3 (2.15%), Enterobacter species 7 (5.03%), Morganella morganii 2 (1.43%), and Acinetobacter 7 (5.03%). Amikacin was the most susceptible antibiotic to the majority of the microorganisms, followed by gentamicin, piperacillin/tazobactam, vancomycin chloramphenicol, and clindamycin. Among the resistant antibiotics, penicillins and cephalosporins were the notable ones.

Conclusions:

This study will decipher the bacteriological profiles among patients of diabetic foot ulcers according to their susceptibility and might be helpful to provide effective treatment.
Acute kidney injury development in polytrauma and the safety of early repeated contrast studies: A retrospective cohort study
Authors: Giles Thomas , Weaver Natasha , Varghese Adrian , Way Teagan L. , Abel Christian , Choi Peter , Briggs Gabrielle D. , Balogh Zsolt J.
Published: July 2022

BACKGROUND

The role of repeat intravenous contrast doses beyond initial contrast imaging in the development of acute kidney injury (AKI) for multiple injury patients admitted to the intensive care unit (ICU) is not fully understood. We hypothesized that additional contrast doses are potentially modifiable risk factors for worse outcomes.

METHODS

An 8-year retrospective study of our institutional prospective postinjury multiple organ failure database was performed. Adult ICU admissions that survived >72 hours with Injury Severity Score (ISS) of >15 were included. Patients were grouped based on number of repeat contrast studies received after initial imaging. Initial vital signs, resuscitation data, and laboratory parameters were collected. Primary outcome was AKI (Kidney Disease: Improving Global Outcomes criteria), and secondary outcomes included contrast-induced acute kidney injury (CI-AKI; >25% or >44 μmol/L increase in creatinine within 72 hours of contrast administration), multiple organ failure, length of stay, and mortality.

RESULTS

Six-hundred sixty-three multiple injury patients (age, 45.3 years [SD, 9.1 years]; males, 75%; ISS, 25 (interquartile range, 20–34); mortality, 5.4%) met the inclusion criteria. The incidence of AKI was 13.4%, and CI-AKI was 14.5%. Multivariate analysis revealed that receiving additional contrast doses within the first 72 hours was not associated with AKI (odds ratio, 1.33; confidence interval, 0.80–2.21; p = 0.273). Risk factors for AKI included higher ISS (p < 0.0007), older age (p = 0.0109), higher heart rate (p = 0.0327), lower systolic blood pressure (p = 0.0007), and deranged baseline blood results including base deficit (p = 0.0042), creatinine (p < 0.0001), lactate (p < 0.0001), and hemoglobin (p = 0.0085). Acute kidney injury was associated with worse outcomes (ICU length of stay: 8 vs. 3 days, p < 0.0001; mortality: 16% vs. 3.8%, p < 0.0001; MOF: 42% vs. 6.6%, p < 0.0001).

CONCLUSION

There is a limited role of repeat contrast administration in AKI development in ICU-admitted multiple injury patients. The clinical significance of CI-AKI is likely overestimated, and it should not compromise essential secondary imaging from the ICU. Further prospective studies are needed to verify our results.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level III.
Presumptive Idiopathic Intracranial Hypertension Based on Neuroimaging Findings: A Referral Pattern Study
Authors: Aung Andre B. , Chen Benson S. , Wicks Jaime , Bruce Beau B. , Meyer Benjamin I. , Dattilo Michael , Kedar Sachin , Saindane Amit , Newman Nancy J. , Biousse Valérie
Published: July 2022

Background:

Radiologic findings of intracranial hypertension (RAD-IH) are common in idiopathic intracranial hypertension (IIH) patients. Paralleling the increasing rates of obesity, the burden of IIH is growing. Urgent neuro-ophthalmology consultations for possible IIH in patients with incidentally detected RAD-IH are increasing, with many patients receiving unnecessary lumbar punctures (LPs) and treatments. This retrospective observational study aimed to determine the prevalence of neuro-ophthalmology consultations for RAD-IH, rate of funduscopic examination by referring providers, prevalence of papilledema, outcomes after neuro-ophthalmic evaluation, and rates of misdiagnosis.

Methods:

Records of 1,262 consecutive new patients seen in one neuro-ophthalmology clinic from January 2019 to January 2020 were reviewed. We identified patients who were: 1) referred with concern for IIH because of findings of RAD-IH; 2) referred for “papilledema”; 3) referred with a diagnosis of IIH; and 4) referred for spontaneous cranial cerebrospinal fluid (CSF) leaks. In addition to basic demographic profiles for all groups, detailed information was collected for patients referred solely for RAD-IH, including referral patterns, prior history of IIH, previous LPs, prior medical or surgical treatment(s), risk factors for increased intracranial pressure (ICP), presenting symptoms, radiologic features observed on neuroimaging, and final disposition. When available, the neuroimaging was reviewed by an expert neuroradiologist.

Results:

Of 1,262 consecutive new patients, 66 (5%) were referred specifically for RAD-IH; most referrals came from neurologists (58%); 8/66 (12%) patients had papilledema; 16/66 (24%) patients had prior LP and 13/66 (20%) were already treated based on MRI findings; and 22/66 (33%) patients had ≤2 RAD-IH. Only 34/66 (52%) of patients referred for RAD-IH had prior funduscopic examinations. We confirmed papilledema in 26/82 (32%) patients referred for “papilledema.” Only 29/83 (35%) patients referred with a diagnosis of IIH had active papilledema, and 3/16 (19%) patients with spontaneous CSF leaks had papilledema. In total, 247/1,262 (20%) new patients were referred to our clinic over 1 year with concern for IIH, among whom only 66 (27%) were confirmed to have active IIH with papilledema.

Conclusions:

One in 5 new patient referrals seen in our neuro-ophthalmology clinic were referred because of concern for increased ICP, but only 1/4 had active papilledema. Most patients referred for isolated RAD-IH do not have papilledema, many having undergone unnecessary LPs and treatments. The burden of these “rule-out IIH” consultations is overwhelming and will only continue to increase with the concurrent rise of obesity and IIH, straining the already limited neuro-ophthalmologic resources available in the US.
Tele–Neuro-Ophthalmology Utilization, Availability, and Attitudes: Update 1 Year Into the COVID-19 Public Health Emergency
Authors: Moss Heather E. , Lai Kevin E. , Ko Melissa W.
Published: July 2022

Background:

Telehealth was rapidly adopted early in the COVID-19 pandemic as a way to provide medical care while reducing risk of SARS-CoV2 transmission. Since then, telehealth utilization has evolved differentially according to subspecialty. This study assessed changes in neuro-ophthalmology during the first year of the COVID-19 pandemic.

Methods:

Telehealth utilization and opinions pre-COVID-19, early pandemic (spring 2020), and 1 year later (spring 2021) were surveyed among practicing neuro-ophthalmologists in and outside the United States using an online platform. Demographics, self-reported utilization, perceived benefits, barriers, and examination suitability were collected over a 2-week period in May 2021.

Results:

A total of 135 practicing neuro-ophthalmologists (81.5% United States, 47.4% females, median age 45–54 years) completed the survey. The proportion of participants using video visits remained elevated during COVID + 1 year (50.8%) compared with pre-COVID (6%, P < 0.0005, McNemar), although decreased compared with early COVID (67%, P < 0.0005). Video visits were the most commonly used methodology. The proportion of participants using remote testing (42.2% vs 46.2%), virtual second opinions (14.5% vs 11.9%, P = 0.45), and eConsults (13.5% vs 16.2%, P = 0.38) remained similar between early and COVID + 1 year (P = 0.25). The majority selected increased access to care, better continuity of care, and enhanced patient appointment efficiency as benefits, whereas reimbursement, liability, disruption of in-person clinic flow, limitations of video examinations, and patient technology use were barriers. Many participants deemed many neuro-ophthalmic examination elements unsuitable when collected during a live video session, although participants believed some examination components could be evaluated adequately through a review of ancillary testing or outside records.

Conclusions:

One year into the COVID-19 pandemic, neuro-ophthalmologists maintained telemedicine utilization at rates higher than prepandemic levels. Tele–neuro-ophthalmology remains a valuable tool in augmenting patient care.
Peripapillary Vessel Density in Relation to Optic Disc Drusen: A Multimodal Optical Coherence Tomography Study
Authors: Lykkebirk Lea , Wessel Lindberg Anne-Sofie , Karlesand Isabelle , Heiberg Mathias , Malmqvist Lasse , Hamann Steffen
Published: July 2022

Background:

Optic disc drusen (ODD) are acellular calcified deposits within the optic nerve head known to cause visual field defects. An emerging gold standard for the diagnosis of ODD is enhanced depth imaging optical coherence tomography (EDI-OCT). The presence of ODD affects the adjacent peripapillary vasculature, which can be visualized using OCT angiography (OCTA). This study investigates the association between peripapillary vessel density and anatomical ODD location and volume using a newly developed method of multimodal OCT.

Methods:

A case–control study with 16 patients diagnosed with ODD in the period 2008–2017 and 24 healthy controls. All patients and controls had EDI-OCT, OCTA, and demographic data collected. Using EDI-OCT and the medical imaging segmentation tool ITK-SNAP, 3-dimensional (3D) visualization of ODD in patients were created. ODD 3D visualization and corresponding OCTA scans were superimposed, making it possible to correlate ODD volume to the peripapillary vessel density in the corresponding modified Garway-Heath segments of the optic disc.

Results:

We found that mean peripapillary vessel density across all modified Garway-Heath segments were lower in ODD patients compared with controls with significant reduction of peripapillary vessel density in the superior segment (P = 0.03) and globally (P = 0.05). A significant inverse proportionality between ODD volume and peripapillary vessel density in the corresponding segment was seen (P = 0.002).

Conclusions:

We found a reduced peripapillary vessel density in regions with close anatomical proximity to ODD and inverse proportionality between ODD volume and peripapillary vessel density.
Extracellular electron transfer capability of oral pathogens Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis
Authors: Naradasu Divya
Published: July 2022

Polymicrobial oral biofilms, which consist of fermentative-bacteria, are associated with periodontitis, gingivitis and cause systemic diseases1. Unlike aerobic-respiration, fermentation does not require electron acceptors like O2; and redox-cycling of biological electron-carriers, like NADH, drives the intracellular oxidation and reduction of organic-substrates2. Thus, the energy gain is potentially lower than that of respiratory metabolism; however, the high pathogenic activity in anaerobic conditions remained ambiguous3. Afew studies have shown that fermentative gut microbes are capable ofreducing external electron acceptors viaextracellular electron transfer (EET)4-7. EET, a phenomenon initially found in environmental-bacteria, where metabolically generated electrons are transferred to external electron-acceptors through an outer-membraneredoxprotein complex8-9. Thus, the pathogens colonization in the human microbiome may be supported by their EET capability and is important to explore such potentiality. Here, we electrochemically characterized oral-biofilm pathogens Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, to examine their EET ability with lactate/glucose. Both strains showed current production on an electrode surface, associated with consumption of substrate10. The addition of antibiotics that suppress the biosynthesis of membrane or protein showed a significant current decrease, demonstrating that current production reflects the cellular-activity. Further, transmission-electron-microscopy of 3,3‡-diaminobenzidine (DAB) stained cells revealed the presence of redox-enzymes on the cell-membrane suggesting a potential EET mechanism via membrane proteins9. These results could be a basis to reevaluate human oral pathogens from an electroactive point of view. The identified EET activity of the two strains can be utilized for an effective test for assessing the impact of antibacterial compounds on the pathogen cellular-activity on an electrode11.
Exploring the mechanisms of immunomodulation by a commensal Clostridium species
Authors: Tan Chin Yee , Surana Neeraj
Published: July 2022

The microbiome is intricately linked to human health and, when dysregulated, can cause disease. It has been shown that specific members of the intestinal microbiota regulate immunity, a finding that offers an approach for treating autoimmune disease through microbiome engineering. In previously published work, we identified Clostridium immunis, a new human-derived commensal bacterial species that protects mice against colitis. To understand the host immunological response to C. immunis, we performed comprehensive flow cytometric analysis of the colonic immune system of C. immunis-treated mice. We observed a significant decrease in the number of group 3 innate lymphoid cells (ILC3s), a rare but critical tissue-resident immune cell population that has been implicated in autoimmune diseases. We hypothesize that C. immunisproduces a bioactive molecule that downregulates ILC3s. To identify the genetic determinants of ILC3 downregulation by C. immunis, we compared the ability of closely related clostridia to modulate ILC3-produced cytokines in a colonic explant model. By excluding genes encoded by two inactive clostridia strains, we managed to identify 40 genes that are associated with ILC3 modulation. We similarly observed that C. immunis culture supernatant contained activity. By excluding genes that have predicted intracellular products, we further narrowed this list to 8 candidate genes. Critically, we have recently developed a method to perform targeted genetic knockouts in C. immunis, and are currently generating mutants for these genes. This work will therefore identify the gene product required for ILC3 modulation and potentially identify novel classes of bacterially derived molecules to treat ILC3-driven disease.
A Fungal Foray in an NHP Gut Microbiome
Authors: James Steve , Parker Aimee , Purse Catherine , Baker Dave , Telatin Andrea , Funnell Simon , Carding Simon
Published: July 2022

The cynomolgus macaque, Macaca fascicularis, is a non-human primate (NHP) widely used in biomedical research as it shares behavioural, genetic, immunological and physiological similarities with humans. These similarities may extend to the enteric microbiome, with some microbial taxa common to both humans and NHPs. However, to date, the majority of these microbial surveys have focused on the prokaryome, and have largely ignored or overlooked the NHP gut mycobiome.

To address this shortfall, we have undertaken a region-by-region taxonomic survey of the cynomolgus intestinal mycobiota, from duodenum to distal colon, of ten captive animals of differing age. Using a high-throughput ITS1 amplicon sequencing-based approach, we found that fungi from the Ascomycota phylum dominate the cynomolgus enteric mycobiota. The budding yeast genus Kazachstania was most abundant, with K. pintolopesii and K. telluris highly prevalent, and the predominant species in many of the intestinal samples. However, while K. pintolopesii was present throughout the primate GI tract, K. telluris was found mainly in the small intestine.

In this study, K. pintolopesii was identified as the dominant enteric fungus in captive cynomolgus macaques. This contrasts with humans, where Candida albicans is a common member of the intestinal microbiota. To our knowledge, this is the first time K. pintolopesii has been identified as a primate gut commensal.
Investigating Gene Regulation by the Tup1-Cyc8 (Ssn6) Complex in the yeast Saccharomyces cerevisiae
Authors: Lee Brenda
Published: July 2022

The Tup1-Cyc8 (Ssn6) co-repressor complex is a powerful epigenetic regulator of genes in the yeast Saccharomyces cerevisiae. The highly conserved complex brings about a repressive chromatin structure at regulatory regions of its target genes or prevents the recruitment of the factors needed for activation of transcription. The FLO family of genes are repressed by the Tup1-Cyc8 complex, these genes encode the proteins required for flocculation, a stress response in yeast where the cells aggregate, or form flocs, to protect cells within the floc. Interestingly each mutant strain (tup1, cyc8 and tup1 cyc8) has a distinct flocculant phenotype. The tup1 strain displays large, dense flocs compared to smaller, more dispersed flocs associated with the cyc8 strain, whereas the tup1 cyc8 strain displays an intermediate flocculant phenotype. RT-qPCR showed that FLO1, considered to be the dominant member of this family of genes, is highly de-repressed in the tup1 and tup1 cyc8 deletion strains. This suggests that Tup1 makes the dominant contribution to repression of this gene. However, this pattern is not seen at all target genes. The results of RNA-Sequencing show a core set of 429 genes significantly upregulated in all three mutant strains. These genes, on average, show the highest de-repression in the cyc8 and tup1 cyc8 mutant strains. Indicating that Cyc8 makes the dominant contribution to repression at the majority of target genes. Together these results indicate that each of the subunits of the Tup1-Cyc8 complex may be dominant in bringing about repression at different sets of genes.
TORC1 regulates actin dynamics to control proteasome homeostasis
Authors: Williams Thomas , Rousseau Adrien
Published: July 2022

The conserved protein kinase complex TORC1 is a central regulator of protein homeostasis. TORC1 is active under nutrient replete, unstressed conditions and promotes bulk protein synthesis, cell growth, and proliferation. Many stresses inactivate TORC1, including nutrient starvation. When TORC1 is inactivated, bulk protein synthesis is inhibited, and stress-responsive protein synthesis activated. Degradation of damaged or unwanted proteins is increased through autophagy activation and enhanced proteasome assembly.

The 26S proteasome is composed of the 20S core particle (CP), capped with one or two 19S regulatory particles (RP). Following TORC1 inhibition, the Mpk1 kinase is activated. Mpk1 facilitates increased translation of proteasome regulatory particle assembly chaperones (RPACs), leading to increased proteasome assembly. The mechanisms underlying the RPAC translation increase remain unclear, however.

Here, we show that actin depolarisation upon TORC1 inhibition causes RPAC mRNAs to associate more with actin patch structures. Increasing this interaction enhances translation further. We identified Ede1 as a protein which binds translating RPAC mRNA and show that Ede1 is required to increase RPAC mRNA association with actin patches, RPAC translation and proteasome assembly upon stress.
COVID-19 Neuropathology: evidence for SARS-CoV-2 invasion of Human Brainstem Nuclei
Authors: Emmi Aron , Rizzo Stefania , Barzon Luisa , Sandre Michele , Carturan Elisa , Sinigaglia Alessandro , Riccetti Silvia , della Barbera Mila , Boscolo-Berto Rafael , Cocco Patrizia , Macchi Veronica , Antonini Angelo , De Gaspari Monica , Basso Cristina , De Caro Raffaele , Porzionato Andrea
Published: July 2022

Neurological manifestations are common in COVID-19, the disease caused by SARS-CoV-2. Despite reports of SARS-CoV-2 detection in the brain and cerebrospinal fluid of COVID-19 patients, it’s still unclear whether the virus can infect the central nervous system, and which neuropathological alterations can be ascribed to viral tropism, rather than immune-mediated mechanisms.

Here, we assess neuropathological alterations in 24 COVID-19 patients and 18 matched controls who died due to pneumonia / respiratory failure. Aside from a wide spectrum of neuropathological alterations, SARS-CoV-2-immunoreactive neurons were detected in specific brainstem nuclei of 5 COVID-19 subjects. Viral RNA was also detected by real-time RT-PCR. Quantification of reactive microglia revealed an anatomically segregated pattern of inflammation within affected brainstem regions, and was higher when compared to controls. While the results of this study support the neuroinvasive potential of SARS-CoV-2, the role of SARS-CoV-2 neurotropism in COVID-19 and its long-term sequelae require further investigation.