Background and purpose KCNQ-encoded KV7 channels are expressed within vascular smooth muscle cells (VSMCs) and are key regulators of vascular reactivity, regulating resting tone and as functional targets of endogenous responses. Endothelial cells (ECs) form a paracrine signaling platform that line all blood vessels and regulate tone, but little is known of KV7 channels in vascular ECs. This study aims to characterize the expression and function of KV7 channels within rat mesenteric artery ECs. Experimental approach In rat mesenteric artery, KCNQ transcript and KV7 channel protein expression were determined via RT-qPCR, immunocytochemistry, immunohistochemistry and immunoelectron microscopy. Wire myography was used to determine vascular reactivity. Key results KCNQ transcript was identified in EC marker expressing cells using a reductive approach. KV7.4 and KV7.5 protein expression was determined in both isolated EC and VSMC and in whole vessels. Removal of ECs attenuated vasorelaxation to two structurally different KV7.2-5 activators S-1 and ML213. KIR2 blockers ML133 and BaCl also attenuated S-1 or ML213-mediated vasorelaxation in an endothelium-dependent process. KV7 inhibition attenuated receptor-dependent nitric oxide (NO)-mediated vasorelaxation to carbachol, but had no impact on relaxation to the NO donor, SNP. Conclusions and implications In rat mesenteric artery ECs, KV7.4 and KV7.5 channels are expressed, functionally interact with endothelial KIR2.x channels and contribute to endogenous eNOS-mediated relaxation. This study identifies KV7 channels as novel functional channels within rat mesenteric ECs and suggests that these channels are involved in NO release from the endothelium.

Background and Purpose: Cancer resistance to chemotherapy is a clinical dilemma that eventually leads to increased mortality. It is widely accepted that cancer stem cells (CSCs) have a pivotal role in the development of resistance. Nonsteroidal anti-inflammatory drugs (NSAIDs) have shown a promise to combat CSCs, thus, we addressed for the first time the effect of indomethacin on cisplatin (CDDP)-resistant murine breast cancer along with the relevant mechanisms. Experimental Approach: The murine mammary adenocarcinoma, Ehrlich ascites carcinoma (EAC) cells, were made resistant by exposure to CDDP and the surviving cells were then analyzed by flow cytometry for the breast CSCs markers (CD44+CD24-). CDDP heavily enriched the CSCs population which was subsequently injected into mice. After induction of tumors, mice were treated with CDDP, or indomethacin, or co-treatment with both drugs, or left untreated. Upon termination of the treatment period, blood samples were collected to measure the percentage of CSCs markers (CD44, CD24, SCa-1) and the immune cells (CD4+, CD62L+, and CD117+). The tumors were excised and analyzed for the relative expression of drug resistance-mediating miRNAs (miR-7, miR-21, miR-22, and miR-145) in addition to histopathological examination. Key Results: Indomethacin drastically diminished the tumorigenicity of CDDP-resistant cells along with enhancing its sensitivity to CDDP which were correlated with its suppressing ability of CD44+CD24- cells and manipulating effect on miRNAs expression. Besides, indomethacin expanded the pool of immune cells that impart antitumor response. Conclusion and Implications: Indomethacin through targeting CSCs may confer better outcome than conventional chemotherapeutics in the treatment of resistant breast cancer.

Background and Purpose: Selective negative allosteric modulators (NAMs), targeting α5 subunit-containing GABAA receptors (GABAARs) as potential therapeutic targets for disorders associated with cognitive deficits, including Alzheimer’s disease (AD), continually fail clinical trials. We investigated whether this was due to the alteration of synaptic mechanisms associated with α5 GABAARs in AD. Experimental approach: Using medicinal chemistry and computational modelling, we developed aqueous soluble hybrids of 6,6-dimethyl-3-(2-hydroxyethyl)thio-1-(thiazol-2-yl)-6,7-dihydro-2-benzothiophen-4(5H)-one, that demonstrated selective binding and high negative allosteric modulation, specifically for the α5 GABAAR subtype in constructed HEK293 stable cell-lines. Using a knock-in mouse model of AD (APPNL-F/NL-F), which expresses a mutant form of human amyloid-β (Aβ), we performed immunofluorescence studies combined with electrophysiological whole-cell recordings to investigate the effects of our key molecule, α5-SOP002 in the hippocampal CA1 region. Key Results: In aged APPNL-F/NL-F mice, a selective preservation of α5 GABAARs was observed in: dis-inhibitory, calretinin- (CR), cholecystokinin- (CCK), somatostatin- (SST) expressing interneurons, and pyramidal cells. Synaptic inhibition recorded from CR interneurons in APPNL-F/NL-F mice, was abnormally excessive, but was “normalised” with bath-applied α5-SOP002 (1 μM). However, α5-SOP002, further impaired inhibition onto CCK and pyramidal cells that were already largely compromised by exhibiting a deficit of inhibition in the AD model. Conclusions and Implications: Using a multi-disciplinary approach, we show that exposure to α5 GABAAR NAMs may further compromise aberrant synapses in AD. We therefore suggest that the α5 GABAAR is not a suitable therapeutic target for the treatment of AD or other cognitive deficits due to the widespread neuronal-networks that use α5 GABAARs.

River network extraction is the basis of hydrological analysis and related issues. The accuracy of river extraction directly affects the accuracy of watershed related research. The key to extracting the river network by using hydrological analysis method is to determine the drainage area threshold. At present, there are existing methods for determining the drainage area threshold, which have problems such as inaccurate extraction with a single threshold and difficulty in obtaining data with multi-threshold. In view of this, based on DEM data of Jiuyuangou watershed in the Loess Plateau, combined hydrological analysis and digital terrain analysis methods, based on the principle of river network extraction from slope runoff, and taking into full consideration the hydrological characteristics of the terrain of the watershed, this paper proposes a threshold determination method based on multi-threshold constraints of local characteristics of the water system and compares the river network accuracy between the river network extracted by the threshold determined by this method and the single t value determination method and the river network extracted by the threshold determined by the river network density method. The results show that among the two river network quantitative indicators including average branch ratio and average length ratio, the corresponding values of the extracted river network by the threshold determined by the multi-threshold constraint method are 4.94 and 9.90, which are the least different from the real river network (4.36 and 9.60), and the other two methods are quite different. The research results show that the river network extracted by the threshold determined by the multi-threshold constraint method can more realistically express the characteristics of the water system, and requires less data, which provides a new idea for determining the optimal the drainage area threshold for the DEM water system.

Title pageFull Title of Manuscript: Neonatal goat’s milk protein allergy – a rare cause for food protein allergyAuthors’ full names: Yee Ian Yik (MBBS, MS, MRCS Ed, Ph.D.)1, Ann Kee How (MBBS, MRCP)2Authors’ Institutional Affiliations: 1Division of Paediatric & Neonatal Surgery, Department of Surgery, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, Malaysia2Cardiology Department, Hospital Serdang, Jalan Puchong, 43000 Kajang, Selangor, Malaysia.Running title: Neonatal goat’s milk protein allergyCorresponding author: Prof. Dr. Yee Ian Yik (MBBS, MS, MRCSEd, Ph.D.)Postal address:Division of Paediatric & Neonatal Surgery, Department of Surgery, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur, MalaysiaFax: +603-79586360Phone: +603-79492441Email:yiyik2003@gmail.comWord count: 905 words; number of figures : 3

Objectives To clarify the clinical features of cured patients with coronavirus disease (COVID-19) and the relevance of IgM and IgG testing. Methods A total of 187 cured COVID-19 patients with antibody test were followed up every two weeks. Assessment for general condition, symptoms, epidemiological contact history, polymerase chain reaction (PCR) assay, and antibody tests were performed and recorded. Information from Guangzhou CDC was also screened. Results The mean follow-up time was 45.7 days. There were 33 (17.6%) patients with negative results for IgG and 35 (18.7%) patients with positive results for IgM. PCR assay was positive in 10 (5.3%) patients during the follow-up. Neither IgG nor IgM results showed a relationship with PCR test results (all P > 0.05). Neither re-infection nor person-to-person transmission was found in the cured patients. Factors associated with appearance of antibody comprised hospitalization days (OR: 1.07, 95%CI: 1.02-1.13, P = 0.004) and antibiotics treatment (OR: 2.78, 95%CI: 1.10-7.01, P = 0.031) . Conclusions In our study, neither re-infection nor person-to-person transmission was found in cured patients with COVID-19. Additionally, neither IgG nor IgM can be used to replace the PCR test in cured patients.

Introduction: The diagnosis of acute viral bronchiolitis (AVB) is primarily based on the findings in pulmonary auscultation. There is no consensus on which auscultatory finding is the most frequent in AVB. This study aims to describe the pulmonary auscultation in a series of patients with AVB and verify its association with age, sex, viral agent, and duration of oxygen therapy. Method: Pulmonary auscultation was recorded in patients hospitalized for AVB between October 2018 and October 2019 using an electronic stethoscope and then parallelly analyzed by two examiners. The effect of other factors such as sex, age, duration of oxygen therapy and etiological agent was analyzed for any possible associations. Results: Of 114 patients, 67 (58.8%) produced wheeze, 43 (37.7%) produced crackles, and 4 (3.5%) had normal auscultation. Wheezing was predominant in male patients while crackling in female patients (67.1% and 52.3%, respectively; p = 0.039). Age had no significant influence on the auscultation pattern (p = 0.054), etiological agent (p = 0.053) and the duration of oxygen therapy (p = 0.877). The median age was higher in patients with parainfluenza compared to those with RSV (6.5 and 4.4 months, respectively; p = 0.044). The duration of oxygen therapy was higher in patients with RSV compared to those with no identified virus (median 5.2 and 2.68 days, respectively; p = 0.018). Conclusions: Wheezing was recorded as the predominant auscultation finding among hospitalized patients with AVB. The type of virus associated with AVB had no influence on the changes in pulmonary auscultation.

Introduction: Tachycardia-induced cardiomyopathy (TCM) has been known for decades as a reversible form of non-ischemic cardiomyopathy. However, its mechanism and properties remain poorly understood. Methods: This retrospective study investigated endomyocardial biopsy samples from 18 patients with TCM and compared them with samples from 170 patients with dilated cardiomyopathy (DCM), and 496 patients with inflammatory cardiomyopathy (ICM). Results: 684 patients with recent-onset heart failure and reduced ejection fraction not caused by valvular or ischemic heart disease were analyzed. In the TCM group, 81% were male, mean age was 60±13 years, and 94% had heart failure symptoms ≥2 NYHA class. At baseline (BL), 78% had atrial fibrillation/flutter, and 11% inappropriate sinus tachycardia, heart rate was higher compared to DCM and ICM patients (122±25 versus 78±21; p<0.001). Mean ejection fraction at BL was lower compared to DCM and ICM (27±12% versus 39.0±14.6%; p=0.001), but improved significantly more during follow-up (FU) (20% versus 6%; p<0.001). At FU, heart rate and presence of sinus rhythm were similar in all groups. 69% of TCM patients underwent electrical cardioversion or ablation. Compared with DCM patients, TCM patients had a stronger myocardial expression of MHC class II and an equal amount of infiltration with T-cells/macrophages. Compared with ICM patients, the presence of T-cells/macrophages was significantly lower in TCM. The marker of apoptosis (caspase 3) was comparably elevated in TCM/ICM patients. Conclusion: TCM is characterized by immuno-histological changes comparable to DCM except for caspase 3 levels, which were similar to those in ICM.

Objectives: Squamous cell carcinoma(SCC) is the most common laryngeal neoplasm. Squamous cell carcinoma variants (vSCC), on the other hand, show different clinical and pathological features than conventional type. The purpose of this study is to analyze the clinical and pathological findings of vSCC of the larynx. Methods: This retrospective study evaluates 110 patients diagnosed with vSCC in our institution between 2006-2017. Treatment of primary and recurrent diseases was evaluated. Overall survival, disease-specific survival and follow-up times were calculated as months. Difference between preoperative and postoperative pathology reports of surgically treated patients were compared. Results: There were 1497 patients diagnosed with laryngeal malignancy and 110 (7,34%) of these patients were diagnosed with vSCC. The most common pathological subgroup was verrucous carcinoma. The best prognosis was found in verrucous carcinoma and the worst was in spindle cell carcinoma. Overall survival rates was 90% and 54.7%, respectively. A group of patients had a preoperative pathological diagnosis, not vSCC, but conventional SCC with the incidence of 38.5-100% according to the histological subtype. This was most common in acantholytic carcinoma, followed by adenosquamous, basaloid and spindle cell carcinoma, respectively. Conclusions: Spindle cell carcinoma and basaloid type squamous cell carcinoma have the worst prognosis and the highest metastatic potential. Patients diagnosed with these two variants should be followed up more cautiously. It should also be kept in mind that the diagnosis of vSCC can be missed in patients diagnosed only with a small tissue biopsy sample.

Objectives: To evaluate the upper airway changes before and after the use of Mandibular Advancement Device (OAm) of the patients with mild to moderate obstructive sleep apnoea hypopnea syndrome (OSAHS) using Cone Beam Computed Tomography (CBCT). Design: Prospective study recruiting patients from February 2015 to January 2017 Settings: Department of Stomatology at Yan’an Hospital Affiliated to Kunming Medical University, China. Participants: PSG confirmed Chinese OSAHS patients. Main outcomes measures: CBCT scans were done before and after the use of OAm to assess the change in the sagittal and coronal diameter, volumetric changes and the change in Minimal Cross-sectional Area (MCA) of different segments of upper airway. Results: A total of 30 patients were included with an average age of 49.53 ± 6.62 years. A significant increase in sagittal and coronal diameter of the lower margin of soft palate and the upper epiglottis was observed except the hard palate plane after OAm (P>0.05). MCA and volume of the posterior soft palate, lingual, epiglottis area and total airway were significantly increased with the use of OAm (P<0.001). Conclusion: OAm is a beneficial device in OSAHS patients as it increases the upper airway area and the volumetric changes thereby reducing the effects of OSAHS.

“TWEETABLE” ABSTRACT: Extramammary Paget’s treatment with imiquimod and photodynamic therapy in combination can be easily tolerated and used safely and effectively.

Objective: To assess the risk of vulvar cancer and precursors in a cohort of women with vulvar lichen planus (LP) and the clinical and therapeutic features of these patients. Design: retrospective case series review Setting: Lower genital tract Unit of a tertiary hospital in Porto, Portugal Participants: 127 women with the diagnosis of vulvar LP, followed in one institution during a period of eleven years - January 2008 until December 2018. Main outcome measures: Demographic and clinical data were evaluated, as well as treatment, follow-up and histology results. Results: A total of 127 women were diagnosed with vulvar LP. The mean follow-up time was 3.90.5 years (range 1-11 years). Ultra-potent topical corticosteroids were first line treatment in 91.8% (n=112), with 32 cases (25.2%) needing an alternative treatment. An overall of 30 biopsies were performed, in 19 women (15%). Vulvar HSIL was diagnosed in 3 (2.4%) women, 2 (1.6%) of which were later diagnosed with vulvar squamous cell carcinoma. No cases of differentiated vulvar intraepithelial neoplasia were observed. Conclusion: Pre-malignant/malignant transformation in women with vulvar LP under surveillance and compliant with treatment is low. A close follow-up appears to be crucial to prevent future malignancy. Biopsies should be performed whenever a suspicious lesion appears during the follow-up.

The use of museum specimens held in natural history repositories for population and conservation genetic research is increasing in tandem with the use of next generation sequencing technologies. Short Tandem Repeats (STRs), or microsatellite loci, are commonly used genetic markers in population and conservation genetic studies. However, they traditionally suffered from a host of issues: fragment size homology, high costs, and low throughput as a result of capillary electrophoresis genotyping and difficulty in reproducibility across laboratories. Next generation sequencing technologies can address these problems, but the incorporation of DNA derived from museum specimens suffers from significant fragmentation and contamination with exogenous DNA. Combatting these issues requires extra measures of stringency in the lab and during data analysis, yet there have not been any studies evaluating microsatellite allelic dropout from museum specimen extracted DNA. In this study, we explore a high throughput sequencing method to evaluate the amount of variation found within museum specimen DNA extracts for previously characterized microsatellites across PCR replicates. We found it useful to classify samples based on quality after replicated PCRs, which determined the rate by which genotypes were accurately recovered. We also found that longer microsatellites performed worse in all museum specimens, so when designing a study invoking museum specimens, short markers (under 250 bp) should be preferentially selected. Allelic dropout rates across loci were dependent on sample quality. The high quality museum specimens performed as well, and recovered nearly as high quality metrics as our tissue sample. Mitochondrial DNA sequences were not predictive of nuclear DNA presence, as all samples recovered cytochrome b fragments yet many lacked microsatellite genotypes, particularly in samples deemed low quality. Based on our results, we have provided a set of best practices for screening, quality assurance, and incorporation of reliable genotypes from museum specimens.

In recent years integration of Human-Robot interaction with speech recognition has gained a lot of pace in the manufacturing industries. Undoubtedly, this bridges the large gap created between the operator and robot by communication’s point of view. Although there are numerous ways in which communication can be established between a human operator and the robot-like, controlling with a teaching pendant, or a joystick. Currently, the robots are controlled semi-autonomously by means of a computer. However, speech and touch [16] are natural ways of communication in humans, where speech recognition, being the best, is heavily researched technology. In this study, we aim at developing a stable and robust speech recognition system to allow humans to communicate with machines (Robotic-arm) in a seamless manner. This paper intends to investigate the potential of the Linear Predictive coding technique to develop a stable and robust HMM-based phoneme speech recognition system for robotics applications. Our system is divided into three segments: a microphone array, a voice module, and a 3-DOF robotic arm (Figure 1). To validate our approach, we have performed tests with simple and complex sentences for various robotics activities like manipulating a cube and pick and place tasks. Moreover, we also analyzed the test results to rectify problems like accuracy, recognition score, etc. Also the paper briefly enumerates the future prospects and applications of our approach.

1. Deep roots have long been thought to allow trees to coexist with shallow-rooted grasses. Due to the difficulties of working belowground, data demonstrating water uptake and niche partitioning are uncommon. 2. We describe tree and grass root distributions using a depth-specific tracer experiment in a subtropical savanna, Kruger National Park, South Africa. The depth-specific tracer experiment was conducted three times during each of two growing seasons. These point-in-time measurements (i.e., tracer-defined root distributions) were then used in a soil water flow model to estimate continuous water uptake by depth and plant growth form (trees and grasses) across the two growing seasons. 3. Most active tree and grass roots were in shallow soils: the mean depth of water uptake was 22 cm for trees and 17 cm for grasses. However, slightly deeper rooting distributions provided trees with 5% more soil water than the grasses in a drier precipitation year, but 13% less water in a wet year. Small differences in rooting distributions also provided both trees and grasses with depths and times at which each rooting distributions (tree or grass) could extract more soil water than the other (i.e., unique hydrological niches of 4 to 13 mm water). 4. The effect of rooting distributions has long been inferred. By quantifying the depth and timing of water uptake, this research demonstrated that even though rooting distributions appeared similar, they provided trees and grasses with more total water, access to a unique hydrologic niche, or both. This approach demonstrated how even small differences in rooting distributions can provide plants with resource niches that can contribute to species coexistence.

background and aim: world health organization (WHO) declared the novel coronavirus 2019 outbreak a pandemic on 11 March 2020. No data have been published so far regarding the COVID-19 patients undergoing cardiovascular surgery. Methods: Medical files of 503 patients undergoing cardiovascular surgery were evaluated. Sixty-four patients (12.7%) was diagnosed as COVID-19 cases after the surgery following getting symptomatic or detection of abnormality in their laboratory results. The valve surgery in one positive COVID-19 case was canceled due to his abnormal laboratory finding and suspicion to COVID-19. The patients’ clinical course and survival status were documented and analyzed. Results: Coronary artery bypass graft (CABG) was the most type of surgery in both positive and negative COVID-19 groups. In-hospital mortality was demonstrated in 6 (9.4%) and 10 (2.3%) patients in positive and negative COVID-19 groups, respectively. CABG had been performed in five COVID-19 deaths while one of the expired cases underwent valve surgery. The median of white blood cell (WBC) count and C-reactive protein (CRP) was higher and the percentage of lymphocyte was lower in patients who expired. Conclusions: We recommend to postpone all elective surgeries till the end of the crisis and limit the surgeries to only emergency situations. In these cases, the patient should be screened and get necessary medications if highly suspected. In borderline surgical indications, especially in individuals with history of contact to infection, we suggest to screen for COVID-19 before the surgery and monitor the patients closely afterward. All health-care staffs should use full personal protective equipment.

Transesophageal echocardiography (TEE) is the gold standard for diagnosing intracardiac masses (1). Sometimes, its unusual location, size, and patient presentation can pose significant diagnostic challenges. Here we report a rare case of large intra-cardiac vegetation mimicking a cardiac tumor.

Background: Ultrasound is frequently used to assess the function of heart and blood vessels. Here, we used ultrasound to evaluate the changes in vascular-graft-related parameters in patients with coronary heart disease before and after in situ left internal mammary artery (IMA) graft and assessed factors affecting blood flow in the graft. Methods: We collected data on 60 patients who underwent coronary artery bypass grafting (CABG) under the same surgeon. All ultrasonic parameters of IMA before and after CABG were measured using Philips EPIQ7 Ultrasound Machine. We then compared changes in all the parameters and assessed factors affecting IMA blood flow. Results: Postoperative IMA had wider luminal diameter than preoperative IMA, higher peak systolic and peak diastolic velocities, reduced resistance index, and significantly greater diastolic velocity-time integral and its fraction. The IMA-left subclavian artery angle was negatively correlated with intraoperative flow of vascular graft, and the blood flow of the graft was significantly higher 1 week postoperatively than it had been during the operation. Conclusions: In situ IMA bypass in CABG patients increased vascular graft luminal diameter and flow, and the angle between IMA and subclavian artery affected the postoperative flow of the vascular graft.

To test the hypothesis whether a lower metabolic rate is expected in cave organisms compared to surface ones due to an adaptation to food scarcity in subterranean environments, we measured the oxygen consumption rates of individuals from hypogean (i.e. subterranean) and epigean (i.e. surface) populations of the troglophilic newt Calotriton asper. We found that epigean individuals exhibit higher rates than hypogean ones and showed that when we acclimated epigean C. asper to cave conditions, these individuals reduced their oxygen consumption. We compared the metabolic levels of hypogean and epigean C. asper acclimated and non-acclimated to the cave, with the obligate cave salamander Proteus anguinus as wells as two epigean species: an urodel (Ambystoma mexicanum) and a fish (Gobio occitaniae). As predicted, we find differences between hypogean and epigean species, and that the troglophilic C. asper exhibited in-between performances. We argue then that this shift of the metabolic level observed between epigean C. asper non-acclimated and acclimated to the cave is not directly due to the food availability in our experiments but to a stasis of the temperature. However we then discuss that this adjustment of the metabolic level under a temperature close to the thermal optimum may secondarly allow individuals to cope with the food limitations of the subterranean environement.

Lamins are intermediate filament protein located in the inner nuclear membrane, which maintains the structural integrity and function of the nucleus. we have examined the possible interactive role of wild as well as mutant type lamin A in connection with telomere repeat binding protein trf2. Briefly, bioinformatic prediction shows that lamin A has strong interaction with telomeric complexes. DNA binding assay confirms the strong interaction between wild type lamin A and telomeric DNA sequences. Loss of 39 amino acids at C-terminal end of lamin A impairs the nuclear structural integrity and induce chromosomal fusion. We conclude that C-terminal 39 amino acids from tail domain of mature lamin A possibly interact with trf2 and telomere, not lamin C and HGPS mutant lamin A.

Background: Cornual (or interstitial pregnancy) is a rare but life-threatening condition with an incidence of about 1-4% of all types of tubal ectopic pregnancies. It can be managed by open and minimally invasive surgical techniques. Therefore, we aim to compare between laparoscopy and traditional open surgery for managing interstitial pregnancy. Methods: We systematically searched PubMed, Scopus, Web of Science, and Cochrane till May 2020 using relevant keywords and screened retrieved studies for eligibility. Data were extracted from the relevant articles and were pooled as mean difference (MD) or relative risk (RR) with a 95% confidence interval (CI), using Review Manager Software for continuous outcomes and OpenMeta [Analyst] software for windows for dichotomous outcomes. Results: We included four studies, three of which provided data eligible for meta-analysis. The duration of postoperative hospital stay was lower in the laparoscopic surgery group (MD = -1.42, 95% CI [-1.72, -0.76], P < 0.0001). There were no significant difference between laparoscopy and traditional open surgery in operative time (MD = -11.22, 95% CI [-42.44, 20], P = 0.48), blood loss (MD = -9.43, 95% CI [-214.18, 195.32], P = 0.93), post and intraoperative complications (RR = 1.543, 95% CI [0.201, 11.849], P = 0.677), and need for blood transfusion (RR = 0.774, 95% CI [0.497, 1.251], P = 0.296). Conclusion: Laparoscopic surgery is associated with lower postoperative hospital stay duration with no difference in terms of operation time, blood loss, post, and intraoperative complications, and need for blood transfusion compared with laparotomy.

Background: A new concept is being advanced to explain undiagnosed chronic pelvic pain, severe dysmenorrhoea, painful uterine contractions, and deep dyspareunia in women, which has been shown to be anatomically negative. Search strategy: In these “endometriosis-like” syndrome situations, there are many pathophysiological arguments supporting the existence of a visceral uterine sensitization syndrome. Data collection and analysis: These arguments are further developed and use central sensitization mechanisms, just like those for irritable bowel syndrome (IBS) or painful bladder syndrome (PBS). The name “painful uterine syndrome” (PUS) has been suggested, and a basis for a PUS diagnostic score has been established. Central sensitization and visceral sensitization mechanisms have been developed. Muscular hypertonia is common in condition of central sensitization and increased uterine contractility has been confirmed using cine magnetic resonance imaging in PUS situations. These findings led to the application of botulinum toxin (BTX) injections under hysteroscopy of the uterine myometrium in PUS. Main results: A pilot study reported the first use of BTX uterine injections under hysteroscopy in PUS and this pilot study has been analysed. It focuses on a simple and reproducible treatment procedure which shows improvement in dysmenorrhoea and dyspareunia as well as improved quality of life scores. Conclusions: Only long-term randomised studies will be able to confirm that BTX injections are useful as a treatment for this condition. The randomised long-term study, Uteroxine, started in 2020 and will shortly release its results.

Growth decoupling can be used to optimize production of biochemicals and proteins in cell factories. Inhibition of excess biomass formation allows for carbon to be utilized efficiently for product formation instead of growth, resulting in increased product yields and titers. Here, we used CRISPR interference (CRISPRi) to increase production of a single domain antibody (sdAb) by inhibiting growth during production. First, we screened 21 sgRNA targets in the purine and pyrimidine biosynthesis pathways, and found that repression of 11 pathway genes led to increased GFP production and decreased growth. The sgRNA targets pyrF, pyrG, and cmk were selected and further used to improve production of two versions of an expression-optimized sdAb. Proteomics analysis of the sdAb-producing pyrF, pyrG, and cmk growth decoupling strains showed significantly decreased RpoS levels and an increase of ribosome-associated proteins, indicating that the growth decoupling strains do not enter stationary phase and maintain their capacity for protein synthesis upon growth inhibition. Finally, sdAb production was scaled up to shake-flask fermentation where the product yield was improved 2.6-fold compared to the control strain with no sgRNA target sequence. An sdAb content of 14.6% was reached in the best-performing pyrG growth decoupling strain.

Coronavirus Disease 19 (COVID-19) is caused by severe acute respiratory coronavirus-2 and has resulted in an unprecedented global pandemic. The adaptations of pregnancy often predispose pregnant women to a more severe course of respiratory illness with the potential for maternal and perinatal morbidity. Thus, national and international guidelines are rapidly being developed to help maintain optimal care throughout pregnancy. Due to the novelty of COVID-19 and limitations of existing data, heterogeneity exists between these guidelines. We aim to review the available evidence for the management of pregnant women with COVID-19 and summarise the recommendations set out by three main institutions.