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Minh Tam Le,1,2 Nguyen Dac Nguyen,1,2 Nhu Quynh Thi Tran,1 Duong Dinh Le,3 Quoc Huy Vu Nguyen,2 Thanh Ngoc Cao1,2 1Center for Reproductive Endocrinology and Infertility, Hue University of Medicine and Pharmacy, Hue University, Hue, Vietnam; 2Department of Obstetrics and Gynecology, Hue University of Medicine and Pharmacy, Hue University, Hue, Vietnam; 3Department of Public Health, Hue University of Medicine and Pharmacy, Hue University, Hue, VietnamCorrespondence: Minh Tam Le, Center for Reproductive Endocrinology and Infertility, Hue University of Medicine and Pharmacy, Hue University, 06 Ngo Quyen street, 53000, Vietnam, Email leminhtam@hueuni.edu.vnObjective: This study aimed to identify the factors that influence follicular output rate (FORT) and follicle-to-oocyte index (FOI) among infertile Vietnamese women, as described by the Poseidon classification of poor responders.Methods: This cross-sectional analysis includes women who received IVF/ICSI treatment at Hue University Hospital, Vietnam, between January 2017 and December 2019. The study population was divided into four groups: Group 1 (age < 35, AFC ≥ 5 and AMH ≥ 1.2 ng/mL, number of oocytes retrieved in the previous cycle ≤ 9), group 2 (age ≥ 35; AFC ≥ 5 and AMH ≥ 1.2 ng/mL, number of oocytes retrieved in the previous cycle ≤ 9), group 3 (age < 35; AFC < 5 and/or AMH < 1.2 ng/mL) and group 4 (age ≥ 35; AFC < 5 and/or AMH < 1.2 ng/mL). All of the patients underwent controlled ovarian stimulation utilizing GnRH antagonist.Results: A total of 243 cases were recruited into groups 1 (n = 44), 2 (n = 33), 3 (n = 54), and 4 (n = 112). There were statistically significant differences between the four groups in terms of age, infertility type, menstrual cycle, body mass index (BMI) and waist-hip ratio (WHR), endocrine tests, and total retrieved oocytes (p 0.05). The average number of oocytes per participant was 7.27, with the highest number occurring in group 1 (10.77) and the lowest occurring in group 4 (5.59). There was a relationship between FORT and BMI (ß: − 0.146, p=0.039), FSH starting dose (ß: 0.146, p=0.030), and AMH (ß:0.166, p=0.015). No statistically significant correlation was detected between FOI and other variables.Conclusion: The starting dose of FSH for ovarian stimulation and AMH concentration were positively associated with FORT in individuals with a poor prognosis, whereas BMI was negatively correlated with FORT; No other parameters were found to correlate with FOI.Keywords: follicular output rate, FORT, follicle-to-oocyte index, FOI, Poseidon, ovarian response

Nguyen Sa Viet Le,1,2 Minh Tam Le,2,3 Nguyen Dac Nguyen,2,3 Nhu Quynh Thi Tran,3 Quoc Huy Vu Nguyen,2 Thanh Ngoc Cao2,3 1Department of Assisted Reproduction, Hue Central Hospital, Hue, Vietnam; 2Department of Obstetrics and Gynecology, Hue University of Medicine and Pharmacy, Hue University, Hue, Vietnam; 3Center for Reproductive Endocrinology and Infertility, Hue University of Medicine and Pharmacy, Hue University, Hue, VietnamCorrespondence: Minh Tam Le Email leminhtam@huemed-univ.edu.vnPurpose: This study was designed to explore the value of ovarian volume (OV) measured by transvaginal ultrasound and its relationship with anthropometry and serum hormonal levels in a polycystic ovary syndrome (PCOS) population.Patients and Methods: A total of 119 women with PCOS from infertile couples were recruited in this cross-sectional study. On days 2– 4 of the menstrual cycle, transvaginal ultrasound examinations were performed, and hormonal profiles were measured. PCOS diagnosis was based on the Rotterdam 2003 criteria and classified into four phenotype groups. The PCOS group (study group) and the non-PCOS group (control group) were compared.Results: The mean age of the participants was 32.66± 4.10 years compared to 33.99± 4.78 years in 273 cases (69.6%) without PCOS. The mean OV was statistically larger in the PCOS group than in the non-PCOS group (7.65± 3.23 mL vs 6.08± 3.67 mL, p < 0.001) and positively correlated with serum anti-Mullerian (AMH) and luteinizing hormone (LH) levels (r=0.30; p < 0.001 and r=0.23; p < 0.001, respectively), and weakly and inversely correlated with age (− 0.182, p < 0.001). The area under the receiver operating characteristic (ROC) curve of OV in the diagnosis of PCOS was 0.613 (0.557– 0.670, 95% CI).Conclusion: The enlarged OV is remarkable in women with PCOS and is related to AMH and LH concentrations. Although the diagnostic potential of PCOS is substantially low, OV alone may contribute to predicting the severity of PCOS and better performance for the diagnosis of PCOS phenotypes.Keywords: ovarian volume, anti-Mullerian hormone, PCOS phenotypes, diagnose, infertility

Objective. This study examined bacterial skin and soft tissue infections (SSTIs) in pediatric patients at a hospital in Vietnam. Methods. An April 2022-June 2023 prospective obsevational study at a Tertiary Paediatric Centre in Vietnam. Results. From We analyzed 87 cases and found that the greatest occurrence rates were reported during the summer season. Common symptoms were fever, edema, and lower leg involvement. Curiously, although blood cultures seldom verified the offender, Staphylococcus aureus was the most common cause. Additionally, the study found that children with infections including pus were administered a more extended course of antibiotics. Approximately one-third of the patients underwent surgical procedures, and most of them were administered intravenous antibiotics. Fortunately, all the youngsters made a full recovery. Conclusions. In summary, the results indicate that children with purulent SSTIs, primarily attributed to Staphylococcus aureus , may need longer courses of antibiotics. Intravenous antibiotic administration emerged as the predominant therapeutic modality., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Global warming, driven by the accumulation of anthropogenic greenhouse gases, particularly CO 2 , in the atmosphere, has garnered significant attention due to its detrimental environmental impacts. To combat this critical issue, the deployment of CO 2 capture and utilization (CCU) strategies has been considered as one of the technology-based solutions, leading to extensive scientific and engineering research. Electrochemical pH-swing (EPS) processes offer a promising approach to diverse CCU pathways, such as the delivery of pure CO 2 gas, the delivery of bicarbonate (e.g., for microalgae cultivation), and the formation of carbonate minerals. In this study, we discuss several CCU pathways using EPS and provide an in-depth analysis of its mechanisms and potential applications, outlining its limitations from both thermodynamic and kinetic standpoints. The EPS process has demonstrated remarkable capabilities, achieving a CO 2 capture efficiency of over 90% and unlocking valuable opportunities for CCU applications. We also develop an initial techno-economic assessment and provide the perspectives and challenges for future development and deployment of EPS. This study sheds light on the integration of EPS with CCU, closing the carbon cycle by effectively utilizing the products generated through the process, such as carbonate minerals and bicarbonate solution. For instance, the bicarbonate product can serve as a viable feedstock for bicarbonate-based microalgae production systems, with the added benefit of reducing costs by 40-80% compared to traditional gaseous CO 2 delivery approaches. By integration of electrochemical technologies with CCU methods, this study underscores the immense potential for mitigating CO 2 emissions and advancing sustainable practices to combat global warming. This study not only addresses the urgent need for effective solutions but also paves the way for a greener and more sustainable future., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Objectives: This study aimed to evaluate the value of anti-Müllerian hormone (AMH) in predicting ovulation induced by aromatase inhibitors (AI) and pregnancy outcomes in women with polycystic ovary syndrome (PCOS)., Methods: From January 2018 to December 2020, this prospective cohort study enrolled women with PCOS aged between 18 and 45 years who underwent ovulation induction using AI protocol and intrauterine insemination (IUI) for infertility at a Center for Reproductive Endocrinology and Infertility, University Hospital. Receiver operating characteristic curves were used to estimate the chance of ovulation responses and pregnancy outcomes., Results: In total, 64% of 65 women with PCOS were recruited following AI treatment, and the clinical pregnancy rate was 19.4% following IUI. Patients who experienced ovulation had a lower mean serum AMH concentration than non-responders (7.11 ng/mL vs. 8.95 ng/mL, respectively), but the difference was not statistically significant. Between the pregnancy and non-pregnancy groups, statistically significant differences in AMH concentrations were observed (8.71 ng/mL vs. 6.73 ng/mL, respectively, P = 0.040). The area under the curve of the receiver operating characteristic for non-ovulation prediction was 0.445, 95% CI (0.284-0.606) with P = 0.467, and for clinical pregnancy was 0.735, 95% CI (0.561-0.910) with P = 0.104., Conclusions: In women with PCOS, the AMH level does not predict ovarian responsiveness to AI treatment, but it does predict the success of IUI cycles., (Copyright © 2023 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Background: Spermatogenesis and sperm quality may be negatively impacted by an increase in reactive oxygen species. This study investigates the efficacy of combined antioxidant therapy for treating male infertility, as measured by semen analyses and the sperm DNA fragmentation index (DFI). Infertile men with a high sperm DNA fragmentation index were instructed to take two oral micronutrient capsules daily for three months. Each antioxidant formulation contained 60 mg vitamin E, 400 µg folic acid, 30 mg selenium, 125 mg L-arginine, 220 mg L-carnitine, 7.5 mg coenzyme Q10, 40 mg L-glutathione, and 20 mg zinc citrate. At entry and post-treatment, the general characteristics, semen analysis, and sperm chromatin dispersion assays were recorded and compared., Results: After three months of treatment with antioxidant compounds, the quality of spermatozoa improved significantly, as indicated by a decrease in the mean DNA fragmentation index from 45.6 ± 17.2% to 34.8 ± 20.3%; an increase in sperm concentration from 29.7 × 10 6 /mL to 35.7 × 10 6 /mL (p < 0.001), an increase in a total number of spermatozoa from 72.1 × 10 6 to 95.5 × 10 6 (p = 0.012), and an increase in the vitality from 75.5 ± 17.1 to 81.1 ± 14.4% viable forms (p < 0.001)., Conclusions: Micronutrient supplementation can improve sperm quality and DNA integrity in infertile men. Men with infertility and significant sperm DNA fragmentation who take antioxidants for three months experience a reduction in DNA fragmentation index and an increase in sperm quality as measured by the semen analysis., Trial Registration: NCT04509583 . Registered 12 August 2020, Hue University of Medicine and Pharmacy Ethics Committee-Retrospectively registered., (© 2023. The Author(s).)

Introduction: This study aimed to determine the predictive value of cancer antigen-125 (CA-125) in combination with serum beta-human chorionic gonadotropin (β-hCG) and progesterone in the early detection of ectopic pregnancy (EP)., Methods: Between May 2019 and May 2020, the cross-sectional study recruited 42 cases of EP and 42 cases of IUP at the same gestational age who visited the Department of Obstetrics and Gynecology, Hospital of Hue University of Medicine and Pharmacy. EP was diagnosed based on surgical (laparoscopy) and postoperative pathology examination., Results: There were significant differences of mean level of β-hCG (2570 mUI/mL vs. 18357.7 mUI/mL), progesterone (10.79 ± 8.16 ng/ml vs. 27.42 ± 4.17 ng/ml) and CA-125 (26.90 ± 10.26 U/mL vs. 70.61 ± 20.89 U/mL) between the EP and the IUP groups (p < 0.001). In the prediction of early diagnosis of EP, the cut-off value of CA-125 at 30.94 U/mL has a sensitivity of 89.3% and a specificity of 87,9%; the cut-off value of β hCG at 2750mIU/ml has the sensitivity of 75%, specificity of 78,8%; the cut-off value of progesterone at 10.24 ng/mL has the sensitivity of 85.7%, specificity of 81.8%. A combination of CA-125, β hCG, and progesterone had a sensitivity of 92.8% and a specificity of 90.9% in early diagnosis of EP., Discussion: Serum CA-125 levels can be used independently or in combination with other markers in the early diagnosis of EP., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Objectives: This study aimed to determine the relationship between oxidative stress (OS) measured by the oxidation-reduction potential (ORP) and the results of semen analysis among men from infertile couples., Methods: This cross-sectional study included 166 men from infertile couples, determined according to the World Health Organization guidelines. The general characteristics, semen analysis, sperm chromatin dispersion assay, and ORP of all subjects were evaluated and analyzed statistically., Results: Among 166 men from infertile couples, individuals with OS had a significantly higher DNA fragmentation index (DFI) than men without OS (22.37% ± 11.67% vs. 17.98% ± 8.98%). The sperm concentration, total sperm count, motility rate, and normal morphology were negatively correlated, while and an abnormal head and neck-tail were positively correlated with ORP. There was also a positive association between the DFI and OS level. The optimal ORP threshold for determining sperm quality was 0.77 mV/10 6 sperm/mL (sensitivity, 50.4%; specificity, 93.5%; positive predictive value, 52.9%; negative predictive value, 32.3%)., Conclusions: Determining the ORP suggests that OS has an adverse effect on the total sperm count, sperm motility, sperm concentration, morphology, vitality, and DNA fragmentation index.

Microbes are a critical component of soil ecosystems, performing crucial functions in biogeochemical cycling, carbon sequestration, and plant health. However, it remains uncertain how their community structure, functioning, and resultant nutrient cycling, including net GHG fluxes, would respond to climate change at different scales. Here, we review global and regional climate change effects on soil microbial community structure and functioning, as well as the climate-microbe feedback and plant-microbe interactions. We also synthesize recent studies on climate change impacts on terrestrial nutrient cycles and GHG fluxes across different climate-sensitive ecosystems. It is generally assumed that climate change factors (e.g., elevated CO 2 and temperature) will have varying impacts on the microbial community structure (e.g., fungi-to-bacteria ratio) and their contribution toward nutrient turnover, with potential interactions that may either enhance or mitigate each other's effects. Such climate change responses, however, are difficult to generalize, even within an ecosystem, since they are subjected to not only a strong regional influence of current ambient environmental and edaphic conditions, historical exposure to fluctuations, and time horizon but also to methodological choices (e.g., network construction). Finally, the potential of chemical intrusions and emerging tools, such as genetically engineered plants and microbes, as mitigation strategies against global change impacts, particularly for agroecosystems, is presented. In a rapidly evolving field, this review identifies the knowledge gaps complicating assessments and predictions of microbial climate responses and hindering the development of effective mitigation strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

For years, agrochemical fertilizers have been used in agriculture for crop production. However, intensive utilization of chemical fertilizers is not an ecological and environmental choice since they are destroying soil health and causing an emerging threat to agricultural production on a global scale. Under the circumstances of the increasing utilization of chemical fertilizers, cultivating microalgae to produce biofertilizers would be a wise solution since desired environmental targets will be obtained including (1) replacing chemical fertilizer while improving crop yields and soil health; (2) reducing the harvest of non-renewable elements from limited natural resources for chemical fertilizers production, and (3) mitigating negative influences of climate change through CO 2 capture through microalgae cultivation. Recent improvements in microalgae-derived-biofertilizer-applied agriculture will be summarized in this review article. At last, the recent challenges of applying biofertilizers will be discussed as well as the perspective regarding the concept of circular bio-economy and sustainable development goals (SDGs)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Chronic venous disease (CVD) and knee osteoarthritis (KOA) are two common diseases in the elderly. Both share common risk factors, such as age, sex, and obesity, and are believed to be associated with inflammatory conditions and venous stasis. However, studies of the association between CVD and KOA are limited, especially in the elderly. To investigate the association between CVD and KOA and their effects on pain and functional status in the elderly at the Rheumatology Clinic of University Medical Center Ho Chi Minh City (HCMC)., Patients and Methods: This cross-sectional study included 222 elderly patients (aged ≥60 years) at the Rheumatology Clinic of University Medical Center HCMC from December 2019 to June 2020, including 167 with and 55 without KOA. Patient data were collected for both groups, including demographics, symptoms, clinical signs, and diagnostic tests for KOA and CVD, including knee radiographs and duplex scanning of the lower extremity veins., Results: CVD was a common comorbidity among elderly patients with KOA (73.65% vs. 58.18%; p = 0.030). CVD symptoms did not differ significantly between patients with and without KOA. After adjusting for age, sex, body mass index, and some comorbid conditions, the differences in CVD incidence between the groups remained significant (odds ratio = 2.46, 95% confidence interval: 1.20-5.06; p = 0.014). Visual Analog Scale and Western Ontario and McMaster Universities Osteoarthritis Index pain scores were higher in elderly patients with KOA and CVD., Conclusions: CVD is common in elderly patients with KOA. While age, sex, and weight are risk factors for both conditions, there is an independent association between them. Patients comorbid with KOA and CVD have more pain and limited functional status.

Laminar-flow microfluidic microbial fuel cell (LMMFC) has attracted attention due to the advantage of the liquid-liquid interface between anolyte and catholyte without the use of membrane as a separator resulting in less fabrication cost. Unlike previous studies of LMMFC using syringe pumps, this study proposes the use of osmotic pumps to feed anolyte and catholyte in the microchannel without any additional power supply. The osmotic pump was constructed with two cylindrical chambers separated by a forward osmosis membrane, with the initial draw solution concentration of 90 g l -1 NaCl. We have, for the first time, demonstrated using the osmotic pumps to deliver both anolyte and catholyte and create co-laminar flow in LMMFC. Under the catholyte and anolyte flow rates of 18 ml/h and 40 ml/h respectively, LMMFC cultivated with Shewanella oneidensis produced the maximum power density of 87 mW m -2 and current density of 747 mA m -2 with the internal resistance of 1660 Ω. Further studies are warranted to develop osmotic pumps-fed LMMFC into a potential platform for portable biosensors., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The discharged saline wastewater has severely influenced the aquatic environment as the treatment performance of many wastewater treatment techniques is limited. In addition, the sources of saline wastewater are also plentiful from agricultural and various industrial fields such as food processing, tannery, pharmaceutical, etc. Although high salinity levels negatively impact the performance of both physicochemical and biological processes, membrane bioreactor (MBR) processes are considered as a potential technology to treat saline wastewater under different salinity levels depending on the adaption of the microbial community. Therefore, this study aims to systematically review the application of MBR widely used in the saline wastewater treatment from the perspectives of microbial structure and treatment efficiencies. At last, the concept of carbon dioxide capture and storage will be proposed for the MBR-treating saline wastewater technologies and considered toward the circular economy with the target of zero emission., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The development of cost-effective and energy-efficient technologies to recover nutrients from digestate is important. Anaerobic digestate can be concentrated into bio-nutrient products through an electrodialysis (ED) process in an energy-efficient manner. Despite recent advances, the operation modes of ED for nutrient recovery from swine digestate are yet to be systematically evaluated from the perspective of energy-water efficiencies, and the determination of optimal operations in ED units is still ambiguous. In this study, two different operating modes of electrodialysis, i.e., constant voltage and constant current, are designed to evaluate the energy efficiency and effectiveness of nutrient recovery from anaerobic swine digestate. The ion removal ratio and current efficiency of the different modes and their associated electromigration performance (e.g., rate constants) are evaluated. The results indicate that the maximum removal efficiency (in terms of electrical conductivity) is 92.8% at a cell voltage of 2.4 V/cell using the constant voltage operation. The current efficiencies of NH 4 + (43‒65%) are higher than that of other ions, such as K + (12‒19%), Cl - (4‒7%), and PO 4 3- (0.1‒1.5%). For nitrogen recovery, the required energy consumption was about 0.24‒15.2 kWh/kg-N (0.86‒54.7 kJ/g-N), corresponding to a removal ratio of ammonium from 70.8% to 99.1%. Based on the experimental data, the optimal operating conditions are identified using response surface models by considering process energy consumption and productivity to deliver energy-efficient nutrient separation. One candidate of the ideal conditions to achieve the total ion removal of ∼93% should be operated at a constant cell voltage of 1.15 V, corresponding to a productivity of 5.24 gal/hr/m 2 at an energy consumption of 0.44 kWh/m 3 . Last, a conceptual design of cascading separation processes is proposed for digestate valorization as biofertilizers, nutrients, organic acids, and reclaimed water. A preliminary benefit-cost evaluation is then performed to evaluate the engineering and economic performance of the developed process for nutrient recovery from swine digestate. This article provides insight into practical large-scale applications of digestate valorization through energy-efficient separation, thereby realizing a circular economy system and a decarbonizing supply chain of bio-nutrients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Objective: To investigate the association between asymptomatic hyperuricemia and knee osteoarthritis in older outpatients in Vietnam., Patients and Methods: This cross-sectional study included 257 older outpatients (195 in the knee osteoarthritis group and 62 in the non-knee osteoarthritis group) aged ≥60 years (mean age 73.31 ± 7.96 years) attending rheumatologic and geriatric clinics from November 2020 to May 2021. Data were collected for both groups, including demographics, symptoms and signs of knee osteoarthritis, serum uric acid levels, and knee radiographs. The association between asymptomatic hyperuricemia and knee osteoarthritis was assessed using logistic regression., Results: The mean serum uric acid level among patients with knee osteoarthritis was higher than that among patients without knee osteoarthritis (6.3 ± 1.74 mg/dl vs. 5.71 ± 1.45 mg/dl, p = 0.017). Hyperuricemia was more common among older outpatients with knee osteoarthritis than among those without knee osteoarthritis (39% vs. 19%, p = 0.005). After adjusting for age, sex, body mass index (BMI), and other comorbidities, the association between asymptomatic hyperuricemia and knee osteoarthritis remained significant (odds ratio [OR] 2.61, 95% confidence interval [CI] 1.22-5.60, p = 0.013). Subgroup analyses were performed according to sex and BMI groups. Significant associations between asymptomatic hyperuricemia and knee osteoarthritis were observed among women (p = 0.017) and among individuals who were underweight-normal-weight according to BMI (p = 0.009)., Conclusions: Asymptomatic hyperuricemia is a common comorbidity among older outpatients with knee osteoarthritis. An independent association was identified between asymptomatic hyperuricemia and knee osteoarthritis among older Vietnamese outpatients, although sex and BMI may be confounding factors that impact this association.

Human papillomavirus (HPV) infection in men is a serious issue because it is associated with genital warts, anogenital cancers, and HPV transmission to their sex partners. This study aimed to investigate the prevalence and genotypes of HPVs in Vietnamese male patients hospitalized with sexually transmitted infection (STI) symptoms between 2016 and 2020 by using polymerase chain reaction and reverse dot blot hybridization analysis. HPV DNA was detected in 191/941 (20.3%) penile cell samples. The HPV patient's mean age was 30.3 in the range of 16- and 69-year-old. The highest HPV prevalence (84.7%) was found in patients between 20- and 39-year-old. A total of 313 HPV genotypes were identified. The multiple-infection rate was 42.9%. The most common high-risk (HR)-HPV genotypes were HPV-16 (8.0%), HPV-51 (7.7%), HPV-52 (4.8%), HPV-56 (4.2%), and HPV-18 (3.8%). Furthermore, HPV-11 and HPV-6 genotypes were the two most common low-risk (LR)-HPV genotypes with the rate of 36.7% and 21.4%, respectively. Notably, HPV-52 was found circulating in Vietnam for the first time. In conclusion, this study results showed that HPV prevalence in Vietnamese male patients was common and diverse. In addition, regarding public health and cancer prevention, the inclusion of the HPV vaccination into the national vaccination program for both men and women is recommended., (© 2021 Wiley Periodicals LLC.)

Introduction: Long term complications of COVID-19, the disease caused by the SARS-CoV-2, involve many organ systems, dramatically worsening the quality of life, and finally contributing to impaired physical functioning. Despite the presence of well-identified pathogenetic mechanisms, the effect of "Long COVID" on sexual health has been only marginally addressed., Objectives: To provide coverage of the current literature on long COVID, its epidemiology, pathophysiology, and relevance for erectile function., Methods: Comprehensive review of literature pertaining to the epidemiology and pathophysiology of long COVID, and its relevance for erectile function., Results: Symptoms of long COVID are highly prevalent and involve almost all systems of the human body, with a plethora of clinical manifestations which range from minor nuisances to life-threatening conditions. "Brain fog" and fatigue are the most common complaints, although other neuropsychiatric complications, including sensory dysfunctions, anxiety, depression, and cerebrovascular events have also been reported. The respiratory and cardiovascular systems are also affected, with dyspnea, pulmonary fibrosis, endothelial dysfunction, and myocarditis occurring in some COVID long haulers. A subset of patients might develop endocrine manifestations, including onset of diabetes, thyroid dysfunction, and hypogonadism. Overall, long COVID features many complications which can impair erectile function by multiple pathogenetic mechanisms, and which could require tailored treatment: (i) careful investigation and management from the sexual medicine expert are therefore much needed, (ii) and future research on this topic is warranted., Conclusion: in COVID-19 long haulers, several complications can adversely affect erectile function which, upon future tailored studies, could be used as biomarker for the severity of the long COVID disease and for its follow-up. Sansone A, Mollaioli D, Limoncin E et al. The Sexual Long COVID (SLC): Erectile Dysfunction as a Biomarker of Systemic Complications for COVID-19 Long Haulers. Sex Med Rev 2022;10:271-285., (Copyright © 2021 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

This paper reports an evaluation of the properties of medium-quality concrete incorporating recycled coarse aggregate (RCA). Concrete specimens were prepared with various percentages of the RCA (25%, 50%, 75%, and 100%). The workability, mechanical properties, and durability in terms of abrasion of cured concrete were examined at different ages. The results reveal insignificant differences between the recycled concrete (RC) and reference concrete in terms of the mechanical and durability-related measurements. Meanwhile, the workability of the RC reduced vastly since the replacement of the RCA reached 75% and 100%. The ultrasound pulse velocity (UPV) results greatly depend on the porosity of concrete and the RC exhibited higher porosity than that of the reference concrete, particularly at the transition zone between the RCA and the new paste. Therefore, the sound transmission in the RC required longer times than that in the reference concrete. Moreover, a predictive equation relating the compressive strength to the UPV was developed.

Nitrification inhibitors (NIs) such as dicyandiamide (DCD), 3,4-dimethylpyrazole phosphate (DMPP), and allylthiourea (AT) are commonly used to suppress ammonia oxidization at different time scales varying from a few hours to several months. Although the responses of NIs to edaphic and temperature conditions have been studied, the influence of the aforementioned factors on their inhibitory effect remains unknown. In this study, laboratory-scale experiments were conducted to assess the short-term (24 h) influence of eight abiotic and biotic factors on the inhibitory effects of DCD, DMPP, and AT across six cropped and non-cropped soils at two temperature conditions with three covariates of soil texture. Simultaneously, the dominant contributions of ammonia-oxidizing archaea (AOA) and bacteria (AOB) to potential ammonia oxidization (PAO) were distinguished using the specific inhibitor 2 phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide (PTIO). Our results revealed that AT demonstrated a considerably greater inhibitory effect (up to 94.9% for an application rate of 75 mg of NI/kg of dry soil) than DCD and DMPP. The inhibitory effect of AT was considerably affected by the relative proportions of silt, sand, and clay in the soil and total PAO. In contrast to previous studies, the inhibitory effects of all three NIs remained largely unaffected by the landcover type and temperature conditions for the incubation period of 24 h. Furthermore, the efficacy of all three tested NIs was not affected by the differential contributions of AOA and AOB to PAO. Collectively, our results suggested a limited influence of temperature on the inhibitory effects of all three NIs but a moderate dependence of AT on the soil texture and PAO. Our findings can enhance the estimation of the inhibitory effect in soil, and pure cultures targeting the AOA and AOB supported ammonia oxidization and, hence, nitrogen dynamics under NI applications.

A simple design of a broadband multifunctional polarization converter using an anisotropic metasurface for X-band application is proposed. The proposed polarization converter consists of a periodic array of the two-corner-cut square patch resonators based on the FR-4 substrate that achieves both cross-polarization and linear-to-circular polarization conversions. The simulated results show that the polarization converter displays the linear cross-polarization conversion in the frequency range from 8 to 12 GHz with the polarization conversion efficiency above 90%. The efficiency is kept higher than 80% with wide incident angle up to 45°. Moreover, the proposed design achieves the linear-to-circular polarization conversion at two frequency bands of 7.42-7.6 GHz and 13-13.56 GHz. A prototype of the proposed polarization converter is fabricated and measured, showing a good agreement between the measured and simulated results. The proposed polarization converter exhibits excellent performances such as simple structure, multifunctional property, and large cost-efficient bandwidth and wide incident angle insensitivity in the linear cross polarization conversion, which can be useful for X-band applications. Furthermore, this structure can be extended to design broadband polarization converters in other frequency bands.

Progressive freezing is a solvent purification technology with low energy requirements and high concentration efficiency. Although these advantages make it a promising technology, the technique has never been explored for draw solution recovery for forward osmosis (FO). Hence, in this study, the progressive freezing process was used to concentrate three common diluted draw solutions: NaCl, MgCl 2 , and EDTA-2Na with different ice front speeds, stirring rates, and initial draw solution concentrations. Effective partition and intrinsic partition constants were also evaluated. The results reveal that the freezing process can achieve a draw solution recovery rate of 99.73%, 99.06%, and 98.65% with NaCl, MgCl 2 , and EDTA-2Na, respectively, using an ice front speed of 0.5 cm/h, a stirring rate of 2.62 m/s, and 30% of percentage of ice phase. Higher concentration efficiency for NaCl and MgCl 2 was achieved due to the high solubility of NaCl and MgCl 2 increased solute diffusion into the liquid phase solutions. The concentration factors for all three draw solutions exceeded 1.9, indicating that the draw solutes could be reused for the FO process. In addition, the two mass transfer coefficients depended on the ice front speed and the stirring rates were also obtained for scaling up the experiment in the future.

Immunodeficiency often coincides with hyperactive immune disorders such as autoimmunity, lymphoproliferation, or atopy, but this coincidence is rarely understood on a molecular level. We describe five patients from four families with immunodeficiency coupled with atopy, lymphoproliferation, and cytokine overproduction harboring mutations in NCKAP1L , which encodes the hematopoietic-specific HEM1 protein. These mutations cause the loss of the HEM1 protein and the WAVE regulatory complex (WRC) or disrupt binding to the WRC regulator, Arf1, thereby impairing actin polymerization, synapse formation, and immune cell migration. Diminished cortical actin networks caused by WRC loss led to uncontrolled cytokine release and immune hyperresponsiveness. HEM1 loss also blocked mechanistic target of rapamycin complex 2 (mTORC2)-dependent AKT phosphorylation, T cell proliferation, and selected effector functions, leading to immunodeficiency. Thus, the evolutionarily conserved HEM1 protein simultaneously regulates filamentous actin (F-actin) and mTORC2 signaling to achieve equipoise in immune responses., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Hemophagocytic lymphohistiocytosis (HLH) is characterized by immune dysregulation due to inadequate restraint of overactivated immune cells and is associated with a variable clinical spectrum having overlap with more common pathophysiologies. HLH is difficult to diagnose and can be part of inflammatory syndromes. Here, we identify a novel hematological/autoinflammatory condition (NOCARH syndrome) in four unrelated patients with superimposable features, including neonatal-onset cytopenia with dyshematopoiesis, autoinflammation, rash, and HLH. Patients shared the same de novo CDC42 mutation (Chr1:22417990C>T, p.R186C) and altered hematopoietic compartment, immune dysregulation, and inflammation. CDC42 mutations had been associated with syndromic neurodevelopmental disorders. In vitro and in vivo assays documented unique effects of p.R186C on CDC42 localization and function, correlating with the distinctiveness of the trait. Emapalumab was critical to the survival of one patient, who underwent successful bone marrow transplantation. Early recognition of the disorder and establishment of treatment followed by bone marrow transplant are important to survival., (© 2019 Lam et al.)

Introduction: The goal of this study was to identify the profile of genital tract infections and their relationship with clinical and demographic parameters as well as tubal diseases among infertile women in Vietnam., Methodology: In this cross-sectional descriptive study, we enrolled 597 women undergoing infertility treatment at the Center for Reproductive Endocrinology and Infertility, Hue University Hospital, Vietnam. All of the study participants were interviewed and examined by a gynecologist. Consecutive tests were then conducted including direct microscopy examination (wet mount and Gram stain), vaginal culture, polymerase chain reaction (PCR) for chlamydia diagnosis from a cervical canal swab, and a blood test for syphilis detection. A hysterosalpingogram (HSG) was carried out to examine the uterine cavity and Fallopian tubes., Results: A gynecologic infection was diagnosed in 43.4% (259/597) of the infertile women. Bacterial vaginosis was the most common condition at 19.6%of the cases. Candida spp., Chlamydia trachomatis, and Trichomonas vaginalis infections accounted for 17.4%, 3.7%, and 0.3%, respectively. Normal HSG results accounted for 87.4% of the women while 5.5% had 2-sided tubal occlusions, 5.4% had 1-sided tubal occlusions, 1.0% had 1-sided hydrosalpinx, and 0.7% had 2-sided hydrosalpinx. There was no significant association between tubal diseases and current infections; however, aerobic vaginitis increased the risk of tubal diseases by 2.4 times., Conclusions: A marked proportion of infertile Vietnamese women have genital tract infections that can significantly influence their reproductive function and performance. These infections should be routinely screened and treated properly to prevent their consequences, such as infertility, which is especially important in developing countries., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2019 Minh Tam Le, Le Na Thi Nguyen, Duong Dinh Le, Quynh Tram Viet Ngo, Chau Anh Thi Nguyen, Bach Hoang Nguyen, Huy Vu Quoc Nguyen, Thanh Ngoc Cao, Andres Salumets, Reet Mandar.)

Objective: Sperm cryopreservation has been widely used in assisted reproductive technology, as it offers great potential for the treatment of some types of male infertility. However, cryopreservation may result in changes in membrane lipid composition and acrosome status, as well as reductions in sperm motility and viability. This study aimed to evaluate sperm DNA fragmentation damage caused by conventional freezing using the sperm chromatin dispersion test., Methods: In total, 120 fresh human semen samples were frozen by conventional methods, using SpermFreeze Solution as a cryoprotectant. Routine semen analysis and a Halosperm test (using the Halosperm kit) were performed on each sample before freezing and after thawing. Semen parameters and sperm DNA fragmentation were compared between these groups., Results: There was a significant decrease in sperm progressive motility, viability, and normal morphology after conventional freezing (32.78%, 79.58%, and 3.87% vs. 16%, 55.99%, and 2.55%, respectively). The sperm head, midpiece, and tail defect rate increased slightly after freezing. Furthermore, the DNA fragmentation index (DFI) was significantly higher after thawing than before freezing (19.21% prior to freezing vs. 22.23% after thawing). Significant increases in the DFI after cryopreservation were observed in samples with both normal and abnormal motility and morphology, as well as in those with normal viability., Conclusion: Conventional freezing seems to damage some sperm parameters, in particular causing a reduction in sperm DNA integrity.

Background: Many bacteria transport cellobiose via a phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS). In Listeria monocytogenes, two pairs of soluble PTS components (EIIACel1/EIIBCel1 and EIIACel2/EIIBCel2) and the permease EIICCel1 were suggested to contribute to cellobiose uptake. Interestingly, utilization of several carbohydrates, including cellobiose, strongly represses virulence gene expression by inhibiting PrfA, the virulence gene activator., Results: The LevR-like transcription regulator CelR activates expression of the cellobiose-induced PTS operons celB1-celC1-celA1, celB2-celA2, and the EIIC-encoding monocistronic celC2. Phosphorylation by P∼His-HPr at His550 activates CelR, whereas phosphorylation by P∼EIIBCel1 or P∼EIIBCel2 at His823 inhibits it. Replacement of His823 with Ala or deletion of both celA or celB genes caused constitutive CelR regulon expression. Mutants lacking EIICCel1, CelR or both EIIACel exhibitedslow cellobiose consumption. Deletion of celC1 or celR prevented virulence gene repression by the disaccharide, but not by glucose and fructose. Surprisingly, deletion of both celA genes caused virulence gene repression even during growth on non-repressing carbohydrates. No cellobiose-related phenotype was found for the celC2 mutant., Conclusion: The two EIIA/BCel pairs are similarly efficient as phosphoryl donors in EIICCel1-catalyzed cellobiose transport and CelR regulation. The permanent virulence gene repression in the celA double mutant further supports a role of PTSCel components in PrfA regulation., (© 2019 S. Karger AG, Basel.)

Objectives: To determine the relationship between maternal serum uric acid levels and fetal/neonatal complications in women with pre-eclampsia/eclampsia, and to establish a predictive threshold value., Methods: A diagnostic test and historical cohort study conducted by prospective cross-sectional data collection on pregnant women with pre-eclampsia/eclampsia at Hue University Hospital, Vietnam, between March 2015 and July 2017. Pre-eclampsia was diagnosed based on ACOG criteria. Serum uric acid levels were measured by enzymatic colorimetric testing using a Cobas c 501 analyzer (Roche Diagnostics, Mannheim, Germany). Fetal complications included intrauterine growth restriction, preterm delivery, fetal death, and neonatal death., Results: There were 205 women enrolled. Serum uric acid at a cutoff of 393 μmol/L is a good predictor of fetal/neonatal complications (AUC 0.752), with 64.4% sensitivity and 79.5% specificity. High uric acid level (≥393 μmol/L) resulted in increased risk of preterm birth (OR 6.367, 95% CI 3.009-13.084), low Apgar scores (OR 5.514, 95% CI 1.877-16.198), intrauterine growth restriction (OR 7.188, 95% CI 3.592-14.382), and neonatal death (OR 7.818, 95% CI 1.614-37.867). There was no relationship between uric acid level and fetal death (OR 1.803, 95% CI 0.355-9.168)., Conclusions: Maternal serum uric acid concentration is a good predictor of fetal/neonatal outcomes in women with pre-eclampsia/eclampsia., (© 2018 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Background: Heterozygous gain-of-function mutations in PI3K110δ lead to lymphadenopathy, lymphoid hyperplasia, EBV and cytomegalovirus viremia, and sinopulmonary infections., Objective: The known role of natural killer (NK) cell function in the control of EBV and cytomegalovirus prompted us to investigate the functional and phenotypic effects of PI3K110δ mutations on NK cell subsets and cytotoxic function., Methods: Mutations in patients were identified by using whole-exome or targeted sequencing. We performed NK cell phenotyping and functional analysis of patients' cells using flow cytometry, standard Cr 51 cytotoxicity assays, and quantitative confocal microscopy., Results: PI3K110δ mutations led to an altered NK cell developmental phenotype and cytotoxic dysfunction. Impaired NK cell cytotoxicity was due to decreased conjugate formation with susceptible target cells and abrogated activation of cell machinery required for target cell killing. These defects were restored partially after initiation of treatment with rapamycin in 3 patients., Conclusion: We describe novel NK cell functional deficiency caused by PI3K110δ mutation, which is a likely contributor to the severe viremia observed in these patients. Rapamycin treatment partially restores NK cell function, providing a further rationale for its use in patients with this disease., (Copyright © 2018 American Academy of Allergy, Asthma & Immunology. All rights reserved.)

The HLH-2004 criteria are used to diagnose hemophagocytic lymphohistiocytosis (HLH), yet concern exists for their misapplication, resulting in suboptimal treatment of some patients. We sought to define the genomic spectrum and associated outcomes of a diverse cohort of children who met the HLH-2004 criteria. Genetic testing was performed clinically or through research-based whole-exome sequencing. Clinical metrics were analyzed with respect to genomic results. Of 122 subjects enrolled over the course of 17 years, 101 subjects received genetic testing. Biallelic familial HLH (fHLH) gene defects were identified in only 19 (19%) and correlated with presentation at younger than 1 year of age ( P < .0001). Digenic fHLH variants were observed but lacked statistical support for disease association. In 28 (58%) of 48 subjects, research whole-exome sequencing analyses successfully identified likely molecular explanations, including underlying primary immunodeficiency diseases, dysregulated immune activation and proliferation disorders, and potentially novel genetic conditions. Two-thirds of patients identified by the HLH-2004 criteria had underlying etiologies for HLH, including genetic defects, autoimmunity, and malignancy. Overall survival was 45%, and increased mortality correlated with HLH triggered by infection or malignancy ( P < .05). Differences in survival did not correlate with genetic profile or extent of therapy. HLH should be conceptualized as a phenotype of critical illness characterized by toxic activation of immune cells from different underlying mechanisms. In most patients with HLH, targeted sequencing of fHLH genes remains insufficient for identifying pathogenic mechanisms. Whole-exome sequencing, however, may identify specific therapeutic opportunities and affect hematopoietic stem cell transplantation options for these patients.

Human NK cell deficiencies are rare yet result in severe and often fatal disease, particularly as a result of viral susceptibility. NK cells develop from hematopoietic stem cells, and few monogenic errors that specifically interrupt NK cell development have been reported. Here we have described biallelic mutations in IRF8, which encodes an interferon regulatory factor, as a cause of familial NK cell deficiency that results in fatal and severe viral disease. Compound heterozygous or homozygous mutations in IRF8 in 3 unrelated families resulted in a paucity of mature CD56dim NK cells and an increase in the frequency of the immature CD56bright NK cells, and this impairment in terminal maturation was also observed in Irf8-/-, but not Irf8+/-, mice. We then determined that impaired maturation was NK cell intrinsic, and gene expression analysis of human NK cell developmental subsets showed that multiple genes were dysregulated by IRF8 mutation. The phenotype was accompanied by deficient NK cell function and was stable over time. Together, these data indicate that human NK cells require IRF8 for development and functional maturation and that dysregulation of this function results in severe human disease, thereby emphasizing a critical role for NK cells in human antiviral defense., Competing Interests: J.R.Lupski has stock ownership in 23andMe, is a paid consultant for Regeneron Pharmaceuticals, has stock options in Lasergen, Inc. is a member of the Scientific Advisory Board of Baylor Genetics, and is a co-inventor on multiple United States and European patents related to molecular diagnostics for inherited neuropathies, eye diseases, and bacterial genomic fingerprinting (5294533; 5306616; 5523217; 5599920; 5667968; 5780223; 6132954; 6713300; 7141420; 7189511; 7192579; 7273698; 7537899; 8129353; 9365899; 0424473; 0610396; 0989805). The Department of Molecular and Human Genetics at Baylor College of Medicine derives revenue from the chromosomal microarray analysis (CMA) and clinical exome sequencing offered in Baylor Genetics (BMGL: http://www.bmgl.com/BMGL/Default.aspx).

Background: Primary immunodeficiency diseases (PIDDs) are clinically and genetically heterogeneous disorders thus far associated with mutations in more than 300 genes. The clinical phenotypes derived from distinct genotypes can overlap. Genetic etiology can be a prognostic indicator of disease severity and can influence treatment decisions., Objective: We sought to investigate the ability of whole-exome screening methods to detect disease-causing variants in patients with PIDDs., Methods: Patients with PIDDs from 278 families from 22 countries were investigated by using whole-exome sequencing. Computational copy number variant (CNV) prediction pipelines and an exome-tiling chromosomal microarray were also applied to identify intragenic CNVs. Analytic approaches initially focused on 475 known or candidate PIDD genes but were nonexclusive and further tailored based on clinical data, family history, and immunophenotyping., Results: A likely molecular diagnosis was achieved in 110 (40%) unrelated probands. Clinical diagnosis was revised in about half (60/110) and management was directly altered in nearly a quarter (26/110) of families based on molecular findings. Twelve PIDD-causing CNVs were detected, including 7 smaller than 30 Kb that would not have been detected with conventional diagnostic CNV arrays., Conclusion: This high-throughput genomic approach enabled detection of disease-related variants in unexpected genes; permitted detection of low-grade constitutional, somatic, and revertant mosaicism; and provided evidence of a mutational burden in mixed PIDD immunophenotypes., (Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Estrogen impacts insulin action and cardiac metabolism, and menopause dramatically increases cardiometabolic risk in women. However, the mechanism(s) of cardiometabolic protection by estrogen remain incompletely understood. Here, we tested the effects of selective activation of E2 receptor alpha (ERα) on systemic metabolism, insulin action, and cardiac mitochondrial function in a mouse model of metabolic dysfunction (ovariectomy [OVX], insulin resistance, hyperlipidemia, and advanced age). Middle-aged (12-month-old) female low-density lipoprotein receptor (Ldlr)(-/-) mice were subjected to OVX or sham surgery and fed "western" high-fat diet (WHFD) for 3 months. Selective ERα activation with 4,4',4″-(4-Propyl-[1H]-pyrazole-1,3,5-triyl) (PPT), prevented weight gain, improved insulin action, and reduced visceral fat accumulation in WHFD-fed OVX mice. PPT treatment also elevated systemic metabolism, increasing oxygen consumption and core body temperature, induced expression of several metabolic genes such as peroxisome proliferator-activated receptor gamma, coactivator 1 alpha, and nuclear respiratory factor 1 in heart, liver, skeletal muscle, and adipose tissue, and increased cardiac mitochondrial function. Taken together, selective activation of ERα with PPT enhances metabolic effects including insulin resistance, whole body energy metabolism, and mitochondrial function in OVX mice with metabolic syndrome., (© 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.)

Mitochondrial dysfunction has been implicated as a cause of energy deprivation in heart failure (HF). Herein, we tested individual and combined effects of two pathogenic factors of nonischemic HF, inhibition of nitric oxide synthesis [with l-N(G)-nitroarginine methyl ester (l-NAME)] and hypertension [with angiotensin II (AngII)], on myocardial mitochondrial function, oxidative stress, and metabolic gene expression. l-NAME and AngII were administered individually and in combination to mice for 5 wk. Although all treatments increased blood pressure and reduced cardiac contractile function, the l-NAME + AngII group was associated with the most severe HF, as characterized by edema, hypertrophy, oxidative stress, increased expression of Nppa and Nppb, and decreased expression of Atp2a2 and Camk2b. l-NAME + AngII-treated mice exhibited robust deterioration of cardiac mitochondrial function, as observed by reduced respiratory control ratios in subsarcolemmal mitochondria and reduced state 3 levels in interfibrillar mitochondria for complex I but not for complex II substrates. Cardiac myofibrils showed reduced ADP-supported and oligomycin-inhibited oxygen consumption. Mitochondrial functional impairment was accompanied by reduced mitochondrial DNA content and activities of pyruvate dehydrogenase and complex I but increased H2O2 production and tissue protein carbonyls in hearts from AngII and l-NAME + AngII groups. Microarray analyses revealed the majority of the gene changes attributed to the l-NAME + AngII group. Pathway analyses indicated significant changes in metabolic pathways, such as oxidative phosphorylation, mitochondrial function, cardiac hypertrophy, and fatty acid metabolism in l-NAME + AngII hearts. We conclude that l-NAME + AngII is associated with impaired mitochondrial respiratory function and increased oxidative stress compared with either l-NAME or AngII alone, resulting in nonischemic HF., (Copyright © 2016 the American Physiological Society.)

Transposon insertion into Listeria monocytogenes lmo2665, which encodes an EIIC of the phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS), was found to prevent D-arabitol utilization. We confirm this result with a deletion mutant and show that Lmo2665 is also required for D-xylitol utilization. We therefore called this protein EIICAxl. Both pentitols are probably catabolized via the pentose phosphate pathway (PPP) because lmo2665 belongs to an operon, which encodes the three PTSAxl components, two sugar-P dehydrogenases, and most PPP enzymes. The two dehydrogenases oxidize the pentitol-phosphates produced during PTS-catalyzed transport to the PPP intermediate xylulose-5-P. L. monocytogenes contains another PTS, which exhibits significant sequence identity to PTSAxl. Its genes are also part of an operon encoding PPP enzymes. Deletion of the EIIC-encoding gene (lmo0508) affected neither D-arabitol nor D-xylitol utilization, although D-arabitol induces the expression of this operon. Both operons are controlled by MtlR/LicR-type transcription activators (Lmo2668 and Lmo0501, respectively). Phosphorylation of Lmo0501 by the soluble PTSAxl components probably explains why D-arabitol also induces the second pentitol operon. Listerial virulence genes are submitted to strong repression by PTS sugars, such as glucose. However, D-arabitol inhibited virulence gene expression only at high concentrations, probably owing to its less efficient utilization compared to glucose., (© 2016 S. Karger AG, Basel.)

Background: This study investigated the prevalence and socio-cultural correlates of postnatal mood disturbance amongst women 18-45 years old in Central Vietnam. Son preference and traditional confinement practices were explored as well as factors such as poverty, parity, family and intimate partner relationships and infant health., Methods: A cross-sectional study was conducted in twelve randomly selected Commune Health Centres from urban and rural districts of Thua Thien Hue Province, Vietnam. Mother-infant dyads one to six months postpartum were invited to participate. Questionnaires from 431 mothers (urban n = 216; rural n = 215) assessed demographic and family characteristics, traditional confinement practices, son preference, infant health and social capital. The Edinburgh Postnatal Depression Scale (EPDS) and WHO5 Wellbeing Index indicated depressive symptoms and emotional wellbeing. Data were analysed using general linear models., Results: Using an EPDS cut-off of 12/13, 18.1% (n = 78, 95% CI 14.6-22.1) of women had depressive symptoms (20.4% urban; 15.8% rural). Contrary to predictions, infant gender and traditional confinement were unrelated to depressive symptoms. Poverty, food insecurity, being frightened of family members, and intimate partner violence increased both depressive symptoms and lowered wellbeing. The first model accounted for 30.2% of the variance in EPDS score and found being frightened of one's husband, husband's unemployment, breastfeeding difficulties, infant diarrhoea, and cognitive social capital were associated with higher EPDS scores. The second model had accounted for 22% of the variance in WHO5 score. Living in Hue city, low education, poor maternal competence and a negative family response to the baby lowered maternal wellbeing., Conclusions: Traditional confinement practices and son preference were not linked to depressive symptoms among mothers, but were correlates of family relationships and wellbeing. Poverty, food insecurity, violence, infant ill health, and discordant intimate and family relationships were linked with depressive symptoms in Central Vietnam.

Bacterial pathogens commonly show intra-species variation in virulence factor expression and often this correlates with pathogenic potential. The group A Streptococcus (GAS) produces a small regulatory RNA (sRNA), FasX, which regulates the expression of pili and the thrombolytic agent streptokinase. As GAS serotypes are polymorphic regarding (a) FasX abundance, (b) the fibronectin, collagen, T-antigen (FCT) region of the genome, which contains the pilus genes (nine different FCT-types), and (c) the streptokinase-encoding gene (ska) sequence (two different alleles), we sought to test whether FasX regulates pilus and streptokinase expression in a serotype-specific manner. Parental, fasX mutant and complemented derivatives of serotype M1 (ska-2, FCT-2), M2 (ska-1, FCT-6), M6 (ska-2, FCT-1) and M28 (ska-1, FCT-4) isolates were compared. While FasX reduced pilus expression in each serotype, the molecular basis differed, as FasX bound, and inhibited the translation of, different FCT-region mRNAs. FasX enhanced streptokinase expression in each serotype, although the degree of regulation varied. Finally, we established that the regulation afforded by FasX enhances GAS virulence, assessed by a model of bacteremia using human plasminogen-expressing mice. Our data are the first to identify and characterize serotype-specific regulation by an sRNA in GAS, and to show an sRNA directly contributes to GAS virulence., (© 2015 John Wiley & Sons Ltd.)

Protein phosphorylation is a major mechanism of signal transduction in bacteria. Here, we analyzed the proteome and phosphoproteome of a wild-type strain of the food-borne pathogen Listeria monocytogenes that was grown in either chemically defined medium or rich medium containing glucose. We then compared these results with those obtained from an isogenic prfA* mutant that produced a constitutively active form of PrfA, the main transcriptional activator of virulence genes. In the prfA* mutant grown in rich medium, we identified 256 peptides that were phosphorylated on serine (S), threonine (T), or tyrosine (Y) residues, with a S/T/Y ratio of 155:75:12. Strikingly, we detected five novel phosphosites on the virulence protein ActA. This protein was known to be phosphorylated by a cellular kinase in the infected host, but phosphorylation by a listerial kinase had not previously been reported. Unexpectedly, SILAC experiments with the prfA* mutant grown in chemically defined medium revealed that, in addition to previously described PrfA-regulated proteins, several other proteins were significantly overproduced, among them were several proteins involved in purine biosynthesis. This work provides new information for our understanding of the correlation among protein phosphorylation, virulence mechanisms, and carbon metabolism.

RNA-based mechanisms of regulation represent a ubiquitous class of regulators that are associated with diverse processes including nutrient sensing, stress response, modulation of horizontal gene transfer, and virulence factor expression. While better studied in Gram-negative bacteria, the literature is replete with examples of the importance of RNA-mediated regulatory mechanisms to the virulence and fitness of Gram-positives. Regulatory RNAs are classified as cis-acting, e.g. riboswitches, which modulate the transcription, translation, or stability of co-transcribed RNA, or trans-acting, e.g. small regulatory RNAs, which target separate mRNAs or proteins. The group A Streptococcus (GAS, Streptococcus pyogenes) is a Gram-positive bacterial pathogen from which several regulatory RNA mechanisms have been characterized. The study of RNA-mediated regulation in GAS has uncovered novel concepts with respect to how small regulatory RNAs may positively regulate target mRNA stability, and to how CRISPR RNAs are processed from longer precursors. This review provides an overview of RNA-mediated regulation in Gram-positive bacteria, and is highlighted with specific examples from GAS research. The key roles that these systems play in regulating bacterial virulence are discussed and future perspectives outlined., (© 2014 John Wiley & Sons Ltd.)

The bacterial phosphoenolpyruvate (PEP):carbohydrate phosphotransferase system (PTS) carries out both catalytic and regulatory functions. It catalyzes the transport and phosphorylation of a variety of sugars and sugar derivatives but also carries out numerous regulatory functions related to carbon, nitrogen, and phosphate metabolism, to chemotaxis, to potassium transport, and to the virulence of certain pathogens. For these different regulatory processes, the signal is provided by the phosphorylation state of the PTS components, which varies according to the availability of PTS substrates and the metabolic state of the cell. PEP acts as phosphoryl donor for enzyme I (EI), which, together with HPr and one of several EIIA and EIIB pairs, forms a phosphorylation cascade which allows phosphorylation of the cognate carbohydrate bound to the membrane-spanning EIIC. HPr of firmicutes and numerous proteobacteria is also phosphorylated in an ATP-dependent reaction catalyzed by the bifunctional HPr kinase/phosphorylase. PTS-mediated regulatory mechanisms are based either on direct phosphorylation of the target protein or on phosphorylation-dependent interactions. For regulation by PTS-mediated phosphorylation, the target proteins either acquired a PTS domain by fusing it to their N or C termini or integrated a specific, conserved PTS regulation domain (PRD) or, alternatively, developed their own specific sites for PTS-mediated phosphorylation. Protein-protein interactions can occur with either phosphorylated or unphosphorylated PTS components and can either stimulate or inhibit the function of the target proteins. This large variety of signal transduction mechanisms allows the PTS to regulate numerous proteins and to form a vast regulatory network responding to the phosphorylation state of various PTS components., (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)

Despite the public health challenges associated with the emergence of new pathogenic bacterial strains and/or serotypes, there is a dearth of information regarding the molecular mechanisms that drive this variation. Here, we began to address the mechanisms behind serotype-specific variation between serotype M1 and M3 strains of the human pathogen Streptococcus pyogenes (the group A Streptococcus [GAS]). Spatially diverse contemporary clinical serotype M3 isolates were discovered to contain identical inactivating mutations within genes encoding two regulatory systems that control the expression of important virulence factors, including the thrombolytic agent streptokinase, the protease inhibitor-binding protein-G-related α2-macroglobulin-binding (GRAB) protein, and the antiphagocytic hyaluronic acid capsule. Subsequent analysis of a larger collection of isolates determined that M3 GAS, since at least the 1920s, has harbored a 4-bp deletion in the fasC gene of the fasBCAX regulatory system and an inactivating polymorphism in the rivR regulator-encoding gene. The fasC and rivR mutations in M3 isolates directly affect the virulence factor profile of M3 GAS, as evident by a reduction in streptokinase expression and an enhancement of GRAB expression. Complementation of the fasC mutation in M3 GAS significantly enhanced levels of the small regulatory RNA FasX, which in turn enhanced streptokinase expression. Complementation of the rivR mutation in M3 GAS restored the regulation of grab mRNA abundance but did not alter capsule mRNA levels. While important, the fasC and rivR mutations do not provide a full explanation for why serotype M3 strains are associated with unusually severe invasive infections; thus, further investigation is warranted.

Numerous bacteria possess transcription activators and antiterminators composed of regulatory domains phosphorylated by components of the phosphoenolpyruvate:sugar phosphotransferase system (PTS). These domains, called PTS regulation domains (PRDs), usually contain two conserved histidines as potential phosphorylation sites. While antiterminators possess two PRDs with four phosphorylation sites, transcription activators contain two PRDs plus two regulatory domains resembling PTS components (EIIA and EIIB). The activity of these transcription regulators is controlled by up to five phosphorylations catalyzed by PTS proteins. Phosphorylation by the general PTS components EI and HPr is usually essential for the activity of PRD-containing transcription regulators, whereas phosphorylation by the sugar-specific components EIIA or EIIB lowers their activity. For a specific regulator, for example the Bacillus subtilis mtl operon activator MtlR, the functional phosphorylation sites can be different in other bacteria and consequently the detailed mode of regulation varies. Some of these transcription regulators are also controlled by an interaction with a sugar-specific EIIB PTS component. The EIIBs are frequently fused to the membrane-spanning EIIC and EIIB-mediated membrane sequestration is sometimes crucial for the control of a transcription regulator. This is also true for the Escherichia coli repressor Mlc, which does not contain a PRD but nevertheless interacts with the EIIB domain of the glucose-specific PTS. In addition, some PRD-containing transcription activators interact with a distinct EIIB protein located in the cytoplasm. The phosphorylation state of the EIIB components, which changes in response to the presence or absence of the corresponding carbon source, affects their interaction with transcription regulators. This article is part of a Special Issue entitled: Inhibitors of Protein Kinases (2012)., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The bacterial pathogen group A Streptococcus (GAS) causes human diseases ranging from self-limiting pharyngitis (also known as strep throat) to severely invasive necrotizing fasciitis (also known as the flesh-eating syndrome). To control virulence factor expression, GAS utilizes both protein- and RNA-based mechanisms of regulation. Here we report that the transcription factor RivR (RofA-like protein IV) negatively regulates the abundance of mRNAs encoding the hyaluronic acid capsule biosynthesis proteins (hasABC; ∼7-fold) and the protein G-related α(2)-macroglobulin-binding protein (grab; ∼29-fold). Our data differ significantly from those of a previous study of the RivR regulon. Given that grab and hasABC are also negatively regulated by the two-component system CovR/S (control of virulence), we tested whether RivR functions through CovR/S. A comparison of riv and cov single and double mutant strains showed that RivR requires CovR activity for grab and hasABC regulation. Analysis of the upstream region of rivR identified a novel promoter the deletion of which reduced rivR mRNA abundance by 70%. A rivR mutant strain had a reduced ability to adhere to human keratinocytes relative to that of the parental and complemented strains, a phenotype that was abolished upon GAS pretreatment with hyaluronidase, highlighting the importance of capsule regulation by RivR during colonization. The rivR mutant strain was also attenuated for virulence in a murine model of bacteremia infection. Thus, we identify RivR as an important regulator of GAS virulence and provide new insight into the regulatory networks controlling virulence factor production in this pathogen.

Diabetic nephropathy is associated with mesangial ECM (extracellular matrix) accumulation. We have shown that AT-1R [Ang II (angiotensin II) type I receptor] signalling induces ECM proteins via transactivation of PI3K (phosphoinositide 3-kinase) in mesangial cells. In the present study, we examined the mechanisms underlying the effect of high ambient glucose on cell proliferation and ECM expansion in a mesangial context. High glucose induced increases in PI3K activity, proliferation and ECM accumulation in mesangial cells. These effects were abrogated by losartan, an AT-1R antagonist, but not by [Sar1,Thr8]-Ang II (Sar is sarcosine), an inactive analogue of Ang II, or by a neutralizing antibody against Ang I/II. Overexpression of a constitutively active PI3Kalpha or AT-1R alone was sufficient to induce similar changes by high glucose. In contrast, overexpression of an inactive AT-1R lowered the basal levels and rendered the cells non-responsive to high glucose. Moreover, cells overexpressing wild-type AT-1R had enhanced sensitivity to acute Ang II stimulation. These cells, however, did not respond to conditioned medium obtained from mesangial cells cultured in high glucose. We further demonstrated that iAng (intracellular Ang II) can be induced by high glucose but only under certain conditions. Efficient suppression of iAng by short hairpin RNA against angiotensinogen, however, did not affect high glucose-induced effects on MES-13 cells. These results suggest that high ambient glucose induces activation of AT-1R in an Ang II-independent manner to transactivate PI3K, resulting in proliferation and ECM accumulation in mesangial cells.