Anxiety in couples undergoing IVF: evidence from E-Freeze randomised controlled trial.

STUDY QUESTION: What are the risk factors and impacts of anxiety in women and men in heterosexual couples undergoing IVF as part of a randomised trial, with a delay in embryo transfer in one arm? SUMMARY ANSWER: Duration of infertility, ethnicity, and male partner's anxiety levels were associated with women's anxiety at the start of treatment, while initial anxiety score, partner's anxiety score at embryo transfer, ethnicity, and clinic location were associated with women's anxiety levels at embryo transfer; although women undergoing IVF were more anxious than their partners for slightly different reasons, their self-reported state anxiety was not associated with achieving clinical pregnancy, nor with switching from delayed frozen embryo transfer to fresh embryo transfer in an IVF trial. WHAT IS KNOWN ALREADY: Use of IVF treatment continues to rise and patients undergoing IVF are anxious. Participating in a randomised controlled trial (RCT) with uncertainty of arm randomisation might increase their anxiety, while a delay in treatment may add further to anxiety. STUDY DESIGN SIZE DURATION: A mixed methods study was conducted using data from the multi-centre E-Freeze RCT cohort conducted across 13 clinics in the UK from 2016 to 2019. A regression analysis on anxiety scores of couples undergoing the IVF trial and a qualitative analysis of participant questionnaires were performed. PARTICIPANTS/MATERIALS SETTING METHODS: Six hundred and four couples participating in the E-Freeze trial, who had at least one useable State-Trait Anxiety Inventory (STAI) State Anxiety subscale (STAI-S) standardised self-report questionnaire for at least one of the partners, were included in the study. STAI-S scores were measured at consent for trial (T1) and again at embryo transfer (T2). Linear and log-binomial regression were used to explore the association between characteristics and STAI-S scores, and the associations between STAI-S scores and non-compliance and clinical pregnancy, respectively. Responses to the open text question were qualitatively analysed inductively using content analysis. MAIN RESULTS AND THE ROLE OF CHANCE: Women's STAI-S scores at T1 (consent) were associated with their ethnicity, duration of infertility, and their male partner's STAI-S score at T1. Women's STAI-S scores at T2 (embryo transfer) were associated with their ethnicity, location of fertility clinic, their STAI-S score at consent, and their male partner's STAI-S score at embryo transfer. The adjusted coefficient (95% CI) for women's STAI-S scores at T2 was -4.75 (-7.29, -2.20, P < 0.001) for ethnic minority versus White, -2.87 (-4.85, -0.89, P = 0.005) for Scotland versus England, 0.47 (0.37, 0.56, P < 0.001) for each point increase in their own score at T1, and 0.30 (0.21, 0.40, P < 0.001) for each point increase in their male partner's score at T2. On average, women had higher STAI-S scores than men at both time points, and a larger increase of scores between the two time points. However, women's STAI-S scores were not associated with either non-compliance with trial allocation in the 'freeze-all' trial arm, or with chances of pregnancy. Both partners, but particularly women, described feeling anxious about the outcome of IVF, with women carrying the added worry of believing that feeling stressed might itself affect the outcome. Participants highlighted the important role of support from staff in helping them to manage their anxiety. LIMITATIONS REASONS FOR CAUTION: Data were not available on education level or social support, which might influence anxiety scores. Men's baseline characteristics were not collected. WIDER IMPLICATIONS OF THE FINDINGS: Identifying couples at increased risk of emotional distress may be improved by using standardised anxiety measures at the start of the fertility treatment. Women can be reassured that their self-reported state anxiety does not affect their chances of achieving clinical pregnancy through IVF, and this may help to reduce anxiety levels. The psychological wellbeing and experiences of couples undergoing IVF could be supported by patient-centred care: making information about the whole process of treatment and choices available to both partners in accessible formats; ensuring interactions with staff are kind and supportive; and acknowledging and addressing the different concerns of women undergoing IVF and their partners. STUDY FUNDING/COMPETING INTERESTS: This study was an NIHR HTA (National Institute for Health and Care Research Health Technology Assessment) funded study. There are no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: ISRCTN registry: ISRCTN61225414.

Transcriptome analysis discloses antioxidant detoxification mechanism of Gracilaria bailinae under different cadmium concentrations and stress durations.

To remedy Cd pollution in the ocean, macroalgae are used as a bioremediation tool because of their ability to absorb and accumulate Cd. Gracilaria bailinae has high economic and ecological value and can survive in Cd contaminated waters; however, the underlying molecular mechanisms remain unclear. In this study, physiological and biochemical indexes were analyzed after 1, 3, 5, or 7 days of Cd2+ exposure; further, the transcriptome of G. bailinae was examined after a 7-day exposure to a Cd2+ culture environment with Cd levels of 0 mg L-1 (cd1, control), 1 mg L-1 (cd2, low concentration), and 2.5 mg L-1 (cd3, high concentration). The results showed that in the cd2 group, G. bailinae maintained a stable RGR that did not differ significantly (P > 0.05) from that of the cd1 group. However, the soluble protein and MDA contents, as well as the activities of SOD, CAT and POD, were significantly increased (P< 0.05) compared to the cd1 group. No significant differences (P > 0.05) were found among the different Cd2+ stress durations. In contrast, compared with the cd1 group, the RGR, soluble protein content, SOD, CAT, and POD activities were significantly decreased (P< 0.05), while the MDA content was significantly increased (P< 0.05) in the cd3 group. Furthermore, significant differences (P< 0.05) were observed among the various tested Cd2+ stress durations within the cd3 group. Compared to the cd1 group, a total of 30,072 DEGs and 21,680 were identified in the cd2 and cd3 treatments, respectively. More up-regulated genes were found in cd2 group than in cd3 group. GO enrichment analysis showed that these genes were related to peptidase activity, endopeptidase activity, ion transport, peptide biosynthetic and metabolism. In addition, DEGs related to histidine metabolism and the stilbene, diarylheptane, and gingerol pathways were significantly up-regulated in the cd2 group compared to the cd3 group, which resulted in enhanced activities of antioxidant enzymes and promoted cell wall regeneration. The results of this study reveal the response mechanism of G. bailinae to Cd2+ stress, providing valuable insights for assessing the bioremediation potential of G. bailinae for Cd-contaminated waters.

Reduced contrast dose for CT head studies during COVID-19-related contrast shortage: Lesson from a crisis.

OBJECTIVE: Intravenous contrast injection protocol for certain CT studies at our institution was revised in June 2022 in response to the global shortage of iohexol. This included CT head studies performed for neuro-navigation (contrast dose from 90 mL to 70 mL). The quality of these studies was assessed. METHODS: Consecutive CT scans before (n = 32) and after (n = 32) contrast dose reduction were reviewed. Demographic data was obtained from the chart. Subjective observations made by two radiologists in consensus included overall study quality (Likert scale of 1 to 5) and lesion location, margins and internal characteristics that were compared with MRI findings (reference standard) using Fisher's exact test. Superior sagittal sinus attenuation, used as an objective measurement of enhancement, and lesion size were compared using Student's t-test. The institutional database was searched for any study requiring repetition or deemed non-diagnostic. RESULTS/DISCUSSION: The average age (61.1 ± 12.7 years and 61.6 ± 14.9 years) and body surface area (BSA) (1.9 ± 0.3 m2 and 1.9 ± 0.02 m2) was not significantly different (p > 0.05) between groups. There was no significant difference (p > 0.05) in objective or subjective enhancement between the two groups. There was no significant difference between CT and MRI for lesion size, location, number, margins and internal enhancement characteristics in the two groups. No study required repetition or was reported as non-diagnostic. There was no adverse comment about study quality in operative notes. CONCLUSION: Reduced contrast dose neuro-navigation CT head studies are not different in quality compared to the conventional studies.

Synthesis and Identification of Heterobivalent Anticancer Compounds Containing Urea and 5-Arylidene-2-Thiohydantoin Motifs.

Urea and thiohydantoin are among the important privileged structures for drug discovery. We have developed a synthetic approach to the high-throughput synthesis of the heterobivalent compounds containing both urea and 5-arylidene-2-thiohydantoin functional groups. This synthetic methodology was applied to the synthesis of a mixture-based library containing a total of 5280 compounds in a positional scanning format. The library was screened for its antiproliferative activity against cancer cells using a tetrazolium dye (MTT) based assay. Deconvolution of the library identified six hit compounds exhibiting moderate inhibitory potency against cancer cell proliferation.

Peptide-derived ligands for the discovery of safer opioid analgesics.

Drugs targeting the µ-opioid receptor (MOR) remain the most efficacious analgesics for the treatment of pain, but activation of MOR with current opioid analgesics also produces harmful side effects, notably physical dependence, addiction, and respiratory depression. Opioid peptides have been accepted as promising candidates for the development of safer and more efficacious analgesics. To develop peptide-based opioid analgesics, strategies such as modification of endogenous opioid peptides, development of multifunctional opioid peptides, G protein-biased opioid peptides, and peripherally restricted opioid peptides have been reported. This review seeks to provide an overview of the opioid peptides that produce potent antinociception with much reduced side effects in animal models and highlight the potential advantages of peptides as safer opioid analgesics.

Identification and Pharmacological Characterization of a Low-Liability Antinociceptive Bifunctional MOR/DOR Cyclic Peptide.

Peptide-based opioid ligands are important candidates for the development of novel, safer, and more effective analgesics to treat pain. To develop peptide-based safer analgesics, we synthesized a mixture-based cyclic pentapeptide library containing a total of 24,624 pentapeptides and screened the mixture-based library samples using a 55 °C warm water tail-withdrawal assay. Using this phenotypic screening approach, we deconvoluted the mixture-based samples to identify a novel cyclic peptide Tyr-[D-Lys-Dap(Ant)-Thr-Gly] (CycloAnt), which produced dose- and time-dependent antinociception with an ED50 (and 95% confidence interval) of 0.70 (0.52-0.97) mg/kg i.p. mediated by the mu-opioid receptor (MOR). Additionally, higher doses (≥3 mg/kg, i.p.) of CycloAnt antagonized delta-opioid receptors (DOR) for at least 3 h. Pharmacological characterization of CycloAnt showed the cyclic peptide did not reduce breathing rate in mice at doses up to 15 times the analgesic ED50 value, and produced dramatically less hyperlocomotion than the MOR agonist, morphine. While chronic administration of CycloAnt resulted in antinociceptive tolerance, it was without opioid-induced hyperalgesia and with significantly reduced signs of naloxone-precipitated withdrawal, which suggested reduced physical dependence compared to morphine. Collectively, the results suggest this dual MOR/DOR multifunctional ligand is an excellent lead for the development of peptide-based safer analgesics.

Pre-operative embolization of a complex systemic to pulmonary vascular malformation.

A 38-year-old male patient presenting with mild exertional dyspnea was noted to have a lingular opacity on chest radiograph. CT of the chest demonstrated an unusual complex inferior lingular vascular malformation with branches arising from the left internal thoracic artery and the left inferior diaphragmatic artery via the celiac artery. There was suspected communication with both pulmonary arterial and venous branches. Following thorough assessment and comprehensive clinical investigation, the patient elected to proceed to definitive surgical management due to potential risk of life-threatening hemoptysis. Interventional radiology performed pre-operative diagnostic angiography and embolization of the systemic feeding arteries. The patient proceeded to have an uncomplicated video-assisted thoracoscopic surgery segmentectomy and was discharged the next day. The patient was asymptomatic at follow-up with complete resolution of the malformation on CT at 6 months. We discuss an uncommon pathology which benefited from multidisciplinary management including successful pre-operative endovascular embolization.

A shift from open to endovascular repair in the treatment of ruptured middle cerebral artery aneurysms: a single institution experience.

PURPOSE: Middle cerebral aneurysms were underrepresented in the two largest trials (BRAT and ISAT) for the treatment of ruptured intracranial aneurysms. Recent institutional series addressing the choice between endovascular or open repair for this subset of aneurysms are few and have not yielded a definitive conclusion. We compare clinical outcomes of patients presenting with acute subarachnoid hemorrhage from ruptured middle cerebral artery aneurysms undergoing either open or endovascular repair. METHODS: We conducted a retrospective review of 138 consecutive patients with ruptured middle cerebral artery aneurysms admitted into our institution from January 2008 to March 2019 to compare endovascular and open surgical outcomes. RESULTS: Of the ruptured middle cerebral artery aneurysms, 57 underwent endovascular repair while 81 were treated with open surgery. Over the study period, there was a notable shift in practice toward more frequent endovascular treatment of ruptured MCA aneurysms (31% in 2008 vs. 91% in 2018). At discharge (49.1% vs 29.6%; p = .002) and at 6 months (84.3% vs 58.6%; p = 0.003), patients who underwent endovascular repair had a higher proportion of patients with good clinical outcomes (mRS 0-2) compared to those undergoing open surgery. Long-term follow-up data (endovascular 54.9 ± 37.9 months vs clipping 18.6 ± 13.4 months) showed no difference in rebleeding (1.8% vs 3.7%, p = 0.642) and retreatment (5.3% vs 3.7%, p = 0.691) in both groups. CONCLUSION: Our series suggests equipoise in the treatment of ruptured middle cerebral artery aneurysms and demonstrates endovascular repair as a potentially feasible treatment strategy. Future randomized trials could clarify the roles of these treatment modalities.

The proximal balloon occlusion together with direct thrombus aspiration (protect plus) technique: Experience at a tertiary comprehensive stroke center.

BACKGROUND: Timely restoration of cerebral blood flow using reperfusion therapy is the most effective maneuver for salvaging penumbra. We re-evaluated the previously described PROTECT (PRoximal balloon Occlusion TogEther with direCt Thrombus aspiration during stent retriever thrombectomy) Plus technique at a tertiary comprehensive stroke center. METHODS: We retrospectively analyzed all patients who underwent mechanical thrombectomy with stentrievers between May 2011 and April 2020. Patients were divided between those who underwent PROTECT Plus and those who did not (proximal balloon occlusion with stent retriever only). We compared the groups in terms of reperfusion, groin to reperfusion time, symptomatic intracranial hemorrhage (sICH), modified Rankin Scale (mRS) score at discharge. RESULTS: Within the study period, 167 (71.4%) PROTECT Plus and 67 (28.6%) non-PROTECT patients which met our inclusion criteria. There was no statistically significant difference in the number of patients with successful reperfusion (mTICI >2b) between the techniques (85.0% vs 82.1%; p = 0.58). The PROTECT Plus group had lower rates of mRS ≤2 at discharge (40.1% vs 57.6%; p = 0.016). The rate of sICH was comparable (p = 0.35) between the PROTECT Plus group (7.2%) and the non-PROTECT group (3.0%). CONCLUSION: The PROTECT Plus technique using a BGC, a distal reperfusion catheter and stent retriever is feasible for recanalization of large vessel occlusions. Successful recanalization, first-pass recanalization and complication rates are similar between PROTECT Plus and non-PROTECT stent retriever techniques. This study adds to an existing body of literature detailing techniques that use both a stent retriever and a distal reperfusion catheter to maximize recanalization for patients with large vessel occlusions.

Effect of multidisciplinary health education based on lifestyle medicine on menopausal syndrome and lifestyle behaviors of menopausal women: A clinical controlled study.

Background: Menopausal women may experience menopausal syndrome and long-term effects caused by low estrogen levels, such as senile dementia and osteoporosis in the elderly. Most menopausal women may have misconceptions about menopause and low use of pharmacological interventions. These misconceptions may damage the quality of life and miss the critical period for preventing senile diseases. Thus, enhancing the awareness of menopausal women regarding psychosocial and physical changes through health education programs was a way to improve positive attitudes toward menopause and make further treatment options. Objectives: This study aimed to evaluate the effect of multidisciplinary health education based on lifestyle medicine on menopausal syndrome and lifestyle behaviors of menopausal women. Methods: The study was conducted in several hospitals in Chongqing, China. The two groups were from different hospitals with similar medical levels in order to reduce information contamination. It was designed as a clinical controlled trial in which the intervention group (n = 100) and control group (n = 87) were matched for age, age at menarche, menopausal symptoms and drug use status at enrollment. Women in the intervention group received multidisciplinary health education based on lifestyle medicine for 2 months while those in the control group received routine outpatient health guidance. Menopausal syndrome, physical activity and dietary status of participants were assessed before and after the intervention. Paired t-tests and Independent-sample t-tests were adopted for comparison within and between groups, respectively, in the normal variables. Wilcoxon signed-rank tests and Mann-Whitney U tests were adopted for comparison within and between group, respectively, in the abnormal variables. Categorical variables were tested using Pearson's χ2. P-value < 0.05 was statistically significant in statistical tests. Results: Post intervention testing indicated that menopausal syndrome of participants was significantly improved in the intervention group compared to the control group (P < 0.001). Between-group comparison showed a significant improvement of weekly energy expenditure of total physical activity (P = 0.001) and participation in exercise (P < 0.001) in the intervention group compared to the control group after the intervention. The dietary status of participants was significantly improved in the intervention group compared to the control group (P < 0.001). In the intervention group, the menopausal syndrome of participants improved more in the hormone drug group than in the non-hormone group (P = 0.007), as did the control group (P = 0.02). In the hormone drug group, the physical activity (P = 0.003) and dietary status (P = 0.001) mproved more in the intervention group than in the control group. Conclusions: The multidisciplinary health education based on lifestyle medicine was effective in improving the menopausal syndrome and healthy lifestyle behaviors of menopausal women. Studies with extended observation period and larger sample size are in need to evaluate the long-term scale-up effects of the multidisciplinary health education.

Disparities in who is asked about their perinatal mental health: an analysis of cross-sectional data from consecutive national maternity surveys.

BACKGROUND: The perinatal period is a vulnerable time, with one in five women experiencing mental health problems. Antenatal and postnatal appointments are key contact points for identifying women in need of support. Since 2014, the UK National Institute for Health and Care Excellence (NICE) has recommended that all women be asked about their mental health at their antenatal booking appointment and early in the postnatal period. The aim of this study was to assess the proportions of women who reported being asked about their mental health during the perinatal period across consecutive national maternity surveys (NMS) in England and to evaluate sociodemographic disparities in who was asked. METHODS: Secondary analysis was performed on cross-sectional data from the NMS in 2014-2020. In each survey, women reported whether they had been asked about their mental health antenatally (during their booking appointment) and postnatally (up to six months after giving birth). The proportions of women in each survey who reported being asked about their mental health were calculated and compared according to key sociodemographic characteristics and across survey years. Logistic regression was conducted to identify disparities in who was asked. RESULTS: The proportion of women who reported being asked about their mental health antenatally increased from 80.3% (95%CI:79.0-81.5) in 2014 to 83.4% (95%CI:82.1-84.7) in 2020, yet the proportion of women who reported being asked postnatally fell from 88.2% (95%CI:87.1-89.3) in 2014 to 73.7% (95%CI:72.2-75.2) in 2020. Ethnic minority women (aOR range:0.20 ~ 0.67) were less likely to report being asked about their mental health antenatally and postnatally across all surveys compared to White women. Women living in less socioeconomically advantaged areas (aOR range:0.65 ~ 0.75) and women living without or separately from a partner (aOR range:0.61 ~ 0.73) were also less likely to report being asked about their mental health, although there was less consistency in these disparities across the antenatal and postnatal periods and across surveys. CONCLUSIONS: Despite NICE recommendations, many women are still not asked about their mental health during the perinatal period, particularly after giving birth. Women from ethnic minority backgrounds are less likely to be asked and these disparities have persisted over time.

A novel G protein-biased agonist at the µ opioid receptor induces substantial receptor desensitisation through G protein-coupled receptor kinase.

BACKGROUND AND PURPOSE: G protein-biased µ opioid receptor agonists have the potential to induce less receptor desensitisation and tolerance than balanced opioids. Here, we investigated if the cyclic endomorphin analogue Tyr-c[D-Lys-Phe-Tyr-Gly] (Compound 1) is a G protein-biased µ agonist and characterised its ability to induce rapid receptor desensitisation in mammalian neurones. EXPERIMENTAL APPROACH: The signalling and trafficking properties of opioids were characterised using bioluminescence resonance energy transfer assays, enzyme-linked immunosorbent assay and phosphosite-specific immunoblotting in human embryonic kidney 293 cells. Desensitisation of opioid-induced currents were studied in rat locus coeruleus neurones using whole-cell patch-clamp electrophysiology. The mechanism of Compound 1-induced µ receptor desensitisation was probed using kinase inhibitors. KEY RESULTS: Compound 1 has similar intrinsic activity for G protein signalling as morphine. As predicted for a G protein-biased µ agonist, Compound 1 induced minimal agonist-induced internalisation and phosphorylation at intracellular µ receptor serine/threonine residues known to be involved in G protein-coupled receptor kinase (GRK)-mediated desensitisation. However, Compound 1 induced robust rapid µ receptor desensitisation in locus coeruleus neurons, to a greater degree than morphine. The extent of Compound 1-induced desensitisation was unaffected by activation or inhibition of protein kinase C (PKC) but was significantly reduced by inhibition of GRK. CONCLUSION AND IMPLICATIONS: Compound 1 is a novel G protein-biased µ agonist that induces substantial rapid receptor desensitisation in mammalian neurons. Surprisingly, Compound 1-induced desensitisation was demonstrated to be GRK dependent despite its G protein bias. Our findings refute the assumption that G protein-biased agonists will evade receptor desensitisation and tolerance. LINKED ARTICLES: This article is part of a themed issue on Advances in Opioid Pharmacology at the Time of the Opioid Epidemic. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.7/issuetoc.

An Evaluation of Different Digestion Methods for the Quantitation of Inorganic Elements in Human Hair Using ICP-MS.

The inorganic elements have unique properties in biochemical processes in humans. An increasing number of pathologies have been associated with essential element ions, such as lead, mercury, and cadmium. Hair has become an attractive clinical specimen for studying the longitudinal exposure to elements from the external environment. Inductively coupled plasma-mass spectrometry (ICP-MS) coupled with nitric acid (HNO3) digestion is the most common approach for determining inorganic elements from human hair. This study aims to optimize the digestion method for the absolute quantitation of 52 elements using ICP-MS, for a large cohort study in human hair. Five different HNO3 (65%) digestion methods were investigated and evaluated for their internal standard solution stability, reproducibility, element coverage, and standard solution recovery efficiency, namely, room temperature for 24 h (RT), 90°C for 4 h (T90), ultrasonic-assisted digestion (UltraS), programmed digestion of microwave digestion (MicroD), and ordinary microwave oven digestion (O-MicroD). Our results demonstrated that O-MicroD, MicroD, and RT were the best performing digestion methods for coefficient of variation (CV) scores, coverage, and recovery efficiency, respectively. In particular, the O-MicroD method detected multiple elements in a small quantity of hair (3 mg), with minimum nitric acid usage (200 µl) and a short digestion time (30 min). The O-MicroD method had excellent reproducibility, as demonstrated by a continuous thousand injections of hair samples with three internal standards (CV: 103Rh = 3.59%, 115In = 3.61%, and 209Bi = 6.31%). Future studies of the elemental content of hair should carefully select their digestion method to meet the primary purpose of their study.

Dielectric dispersion characteristics of the phospholipid bilayer with subnanometer resolution from terahertz to mid-infrared.

There is growing interest in whether the myelinated nerve fiber acts as a dielectric waveguide to propagate terahertz to mid-infrared electromagnetic waves, which are presumed stable signal carrier for neurotransmission. The myelin sheath is formed as a multilamellar biomembrane structure, hence insights into the dielectric properties of the phospholipid bilayer is essential for a complete understanding of the myelinated fiber functioning. In this work, by means of atomistic molecular dynamics simulations of the dimyristoylphosphatidylcholine (DMPC) bilayer in water and numerical calculations of carefully layered molecules along with calibration of optical dielectric constants, we for the first time demonstrate the spatially resolved (in sub-nm) dielectric spectrum of the phospholipid bilayer in a remarkably wide range from terahertz to mid-infrared. More specifically, the membrane head regions exhibit both larger real and imaginary permittivities than that of the tail counterparts in the majority of the 1-100 THz band. In addition, the spatial variation of dielectric properties suggests advantageous propagation characteristics of the phospholipid bilayer in a relatively wide band of 55-85 THz, where the electromagnetic waves are well confined within the head regions.

Infection complications after transrectal ultrasound-guided prostate biopsy: A radiology department's experience and strategy for improvement.

INTRODUCTION: Transrectal ultrasound (TRUS)-guided prostate biopsy is a common procedure performed to diagnose prostate cancer. The risk of infection complications is well-described in the literature, and strategies to avoid such complications continue to evolve over time. We performed a retrospective review of our infection complications and propose a strategy for improvement. METHODS: We reviewed clinical outcomes from patients undergoing TRUS-guided prostate biopsy at our institution from November 2018 to November 2020. We reported the antimicrobial prophylaxis received, whether the biopsy was systematic or targeted, and we examined the rate of clinically significant infection complications and hospitalization. RESULTS: Among 312 men who underwent TRUS-guided prostate biopsy during the study period, seven (2.2%) had an infection. Four patient groups with distinct antimicrobial regimen were identified; the largest of these patient groups received a three-day course of cefixime and a single dose of fosfomycin (59%). The proportion of patients with infection complications across these groups did not demonstrate a statistically significant difference (p=0.803). There was no significant difference in proportion of infection between systematic and targeted biopsy groups (3.0% vs. 0%, p=0.204). The proportion of patients hospitalized was 1.3%, with a mean length of stay of four days. CONCLUSIONS: We report a rate of clinically significant infection following TRUS-guided prostate biopsy of 2.2%. Due to our referral pathway, we have an inconsistent approach to antimicrobial prophylaxis, although there was no statistically significant difference in infection rate between the groups. We propose a standardized approach that may lead to improved patient outcomes.

Effects of Qihuang Needling on Motor Function for Patients With Parkinson's Disease: Study Protocol for a Multicenter, Randomized Controlled Trial.

Background: Although significant progress has been made in the pharmacologic management of Parkinson's Disease (PD), effective management of movement disorders is still a hurdle for therapeutics targeting PD. Acupuncture is one therapeutic option that could potentially improve the motor function of PD and is widely used as adjuvant therapy. Among the various acupuncture approaches, Qihuang Needling (QHN) therapy has been found to improve motor-function control for patients with PD. However, evidence regarding its efficacy remains scarce. Therefore, to address this need, this study will determine the effects of QHN therapy on motor function in patients with PD and compare it to placebo effects. Methods: This trial is a multicenter, prospective randomized controlled clinical trial. We randomly allocated 144 participants to two groups of 72 patients. Patients in the treatment group were treated with QHN therapy. The control group had undergone insertion of acupuncture needles at sham acupoints not corresponded to acupuncture points. Participants in the verum treatment group and sham-acupuncture control group received 9 sessions over 6 weeks followed by 8 weeks of follow-up. The primary outcome was the change of motor function from baseline to weeks 6 and 14 measured by the PD Rating Scale-Part III Motor Examination (UPDRS-III). Secondary outcome measures included the change of PD daily quality of life-39 (PDQ-39) and Non-Motor Symptoms Scale for PD (NMSS) from baseline to weeks 6 and 14. Discussion: The results of this trial will generate data to improve our general understanding of the efficacy of QHN therapy on motor function in patients with PD and thoroughly compare these responses to the placebo effect. Trial Registration: The trial was registered at the Chinese Clinical Trials Registry (ChiCTR- 2000030871) on 16 March 2020.

The association between conception history and subsequent postpartum depression and/or anxiety: Evidence from the Clinical Practice Research Datalink 1991-2013.

BACKGROUND: Infertility, and fertility treatment, are associated with psychological distress that may influence subsequent mental health including postpartum depression and anxiety. METHODS: Data for women who had a livebirth between 1991 and 2013 were drawn from the Clinical Practice Research Datalink. Conception history prior to their first recorded birth was categorised as 'no fertility problems', 'untreated subfertility', ovulation induction (OI), and assisted reproductive technologies (ART). Depression and/or anxiety in the 12 months postpartum were identified using records of diagnoses, symptoms, and prescriptions. Prevalence was compared, and odds ratios estimated using multivariable logistic regression. RESULTS: Of 235,127 mothers, 31,947 (13.6%) had evidence of postpartum depression and/or anxiety. Mothers in the ART group had 22% lower odds of postnatal depression and/or anxiety compared to mothers in the fertile group (OR 0.78; 95% CI [0.70-0.86]; p < 0.0001). Accounting for prior mental health, lifestyle, sociodemographic and pregnancy-related factors reduced the strength of the association (aOR 0.87; 95% CI [0.78-0.97]; p = 0.01). There were no significant associations observed in the untreated subfertility or OI groups. LIMITATIONS: As in any analysis of routine data, the quality of recording is important and some information was unavailable (e.g. education, social support). CONCLUSIONS: Women with a history of subfertility, OI or ART treatment were not at increased risk of postpartum depression and/or anxiety compared to those with no fertility problems. It is important to explore whether women who underwent ART are less likely to experience depression/anxiety or do not seek help when needed, with implications for their health and care.

Physicochemical Insights on Terahertz Wave Diminished Side Effects of Drugs from Slow Dissociation.

Dopamine D2 receptors (D2Rs) are one of the most intensely investigated and well-established drug targets for neuropsychiatric disorders. Selective D2R antagonists have been developed as efficacious antipsychotic drugs. Nevertheless, the potent drugs with necessarily high affinity are prone to slow dissociation, which invokes a plethora of severe side effects such as extrapyramidal symptoms, substantial weight gain, associated diabetes, etc. This has become a major barrier in treating psychiatric patients. In this work, we propose a physical method, terahertz wave modulation, to promote the dissociation of high-affinity antipsychotics and thus diminish the side effects. We have proven that a 4.0 THz wave could reduce the affinity by 71% between the D2R and a risperidone ligand and meanwhile expand the exit via conformation modulation, which promises an accelerated dissociation of risperidone. In addition, it is estimated that the enhancement of the dissociation rate due to lowered binding by terahertz irritation could constitute up to 8 orders of magnitude, which is fairly impressive and resembles the enzyme's catalysis. Also, acceleration of the dissociation rate could be adjusted by the irritation strength. This work elaborates the terahertz wave-modulated noncovalent interactions critical in cell signaling pathways. Most importantly, it demonstrates the feasibility of terahertz technologies intervening in receptor-ligand complex regulated diseases such as neurodegenerative disorders, metabolic diseases, etc.

Filamentous prophage capsid proteins contribute to superinfection exclusion and phage defence in Pseudomonas aeruginosa.

Filamentous prophages in Pseudomonas aeruginosa PAO1 are converted to superinfective phage virions during biofilm development. Superinfection exclusion is necessary for the development of resistance against superinfective phage virions in host cells. However, the molecular mechanisms underlying the exclusion of superinfective Pf phages are unknown. In this study, we found that filamentous prophage-encoded structural proteins allow exclusion of superinfective Pf phages by interfering with type IV pilus (T4P) function. Specifically, the phage minor capsid protein pVII inhibits Pf phage adsorption by interacting with PilC and PilJ of T4P, and overproduction of pVII completely abrogates twitching motility. The minor capsid protein pIII provides partial superinfection exclusion and interacts with the PilJ and TolR/TolA proteins. Furthermore, pVII provides full host protection against infection by pilus-dependent lytic phages, and pIII provides partial protection against infection by pilus-independent lytic phages. Considering that filamentous prophages are common in clinical Pseudomonas isolates and their induction is often activated during biofilm formation, this study suggests the need to rethink the strategy of using lytic phages to treat P. aeruginosa biofilm-related infections.

Inflammatory Biomarkers and Intracranial Hemorrhage after Endovascular Thrombectomy.

BACKGROUND: Intracranial hemorrhage after endovascular thrombectomy is associated with poorer prognosis compared with those who do not develop the complication. Our study aims to determine predictors of post-EVT hemorrhage - more specifically, inflammatory biomarkers present in baseline serology. METHODS: We performed a retrospective review of consecutive patients treated with EVT for acute large vessel ischemic stroke. The primary outcome of the study is the presence of ICH on the post-EVT scan. We used four definitions: the SITS-MOST criteria, the NINDS criteria, asymptomatic hemorrhage, and overall hemorrhage. We identified nonredundant predictors of outcome using backward elimination based on Akaike Information Criteria. We then assessed prediction accuracy using area under the receiver operating curve. Then we implemented variable importance ranking from logistic regression models using the drop in Naegelkerke R2 with the exclusion of each predictor. RESULTS: Our study demonstrates a 6.3% SITS (16/252) and 10.0% NINDS (25/252) sICH rate, as well as a 19.4% asymptomatic (49/252) and 29.4% (74/252) overall hemorrhage rate. Serologic markers that demonstrated association with post-EVT hemorrhage were: low lymphocyte count (SITS), high neutrophil count (NINDS, overall hemorrhage), low platelet to lymphocyte ratio (NINDS), and low total WBC (NINDS, asymptomatic hemorrhage). CONCLUSION: Higher neutrophil counts, low WBC counts, low lymphocyte counts, and low platelet to lymphoycyte ratio were baseline serology biomarkers that were associated with post-EVT hemorrhage. Our findings, particularly the association of diabetes mellitus and high neutrophil, support experimental data on the role of thromboinflammation in hemorrhagic transformation of large vessel occlusions.