Mastitis and Mammary Abscess Management Audit (MAMMA) in the UK and Ireland.

BACKGROUND: The aim of this multicentre prospective audit was to describe the current practice in the management of mastitis and breast abscesses in the UK and Ireland, with a specific focus on rates of surgical intervention. METHODS: This audit was conducted in two phases from August 2020 to August 2021; a phase 1 practice survey and a phase 2 prospective audit. Primary outcome measurements for phase 2 included patient management pathway characteristics and treatment type (medical/radiological/surgical). RESULTS: A total of 69 hospitals participated in phase 2 (1312 patients). The key findings were a high overall rate of incision and drainage (21.0 per cent) and a lower than anticipated proportion of ultrasound-guided aspiration of breast abscesses (61.0 per cent). Significant variations were observed regarding the rate of incision and drainage (range 0-100 per cent; P < 0.001) and the rate of needle aspiration (range 12.5-100 per cent; P < 0.001) between individual units. Overall, 22.5 per cent of patients were admitted for inpatient treatment, out of whom which 72.9 per cent were commenced on intravenous antibiotics. The odds of undergoing incision and drainage for a breast abscess or being admitted for inpatient treatment were significantly higher if patients presented at the weekend compared with a weekday (P ≤ 0.023). Breast specialists reviewed 40.9 per cent of all patients directly, despite the majority of patients (74.2 per cent) presenting within working hours on weekdays. CONCLUSIONS: Variation in practice exists in the management of mastitis and breast abscesses, with high rates of incision and drainage in certain regions of the UK. There is an urgent need for a national best-practice toolbox to minimize practice variation and standardize patient care.

Mastitis and breast abscess is a painful infection of the breast. It is an extremely common breast problem. One in three women can get this condition at some stage in their life. To treat a breast abscess, the pus inside should be drained out of the body. This can be done either by cutting into the breast using surgery or by inserting a fine needle using an ultrasonography scan (which uses ultrasound). Fine-needle drainage has the benefit that it does not require admission to hospital. Surgery can cause the breast to look misshapen. It is unknown which method is used more often in the UK and Ireland. The aim of this study was to describe how mastitis and breast abscesses are treated in the UK and Ireland. This study involved a survey of practice (phase 1) and collection of data, which are routinely recorded for these patients (phase 2). This study involved 69 hospitals and 1312 patient records. One in five women had an operation for a breast abscess. This was higher than expected. Six in 10 women had a pus drainage using a fine needle. The chance of having an operation depended on the hospital. Women that came to hospital at the weekend were almost twice as likely to have an operation. One in five women were admitted to hospital. The chances of that more than doubled if a woman came to hospital at the weekend. There are differences in treatment of mastitis and breast abscesses across the UK and Ireland. Changes need to be put in place to make access to treatment more equal.

A method for estimating and characterizing explicitly nonlinear dynamic functional network connectivity in resting-state fMRI data.

The past 10 years have seen an explosion of approaches that focus on the study of time-resolved change in functional connectivity (FC). FC characterization among networks at a whole-brain level is frequently termed functional network connectivity (FNC). Time-resolved or dynamic functional network connectivity (dFNC) focuses on the estimation of transient, recurring, whole-brain patterns of FNC. While most approaches in this area have attempted to capture dynamic linear correlation, we are particularly interested in whether explicitly nonlinear relationships, above and beyond linear, are present and contain unique information. This study thus proposes an approach to assess explicitly nonlinear dynamic functional network connectivity (EN dFNC) derived from the relationship among independent component analysis time courses. Linear relationships were removed at each time point to evaluate, typically ignored, explicitly nonlinear dFNC using normalized mutual information (NMI). Simulations showed the proposed method estimated explicitly nonlinearity over time, even within relatively short windows of data. We then, applied our approach on 151 schizophrenia patients, and 163 healthy controls fMRI data and found three unique, highly structured, mostly long-range, functional states that also showed significant group differences. In particular, explicitly nonlinear relationships tend to be more widespread than linear ones. Results also highlighted a state with long range connections to the visual domain, which were significantly reduced in schizophrenia. Overall, this work suggests that quantifying EN dFNC may provide a complementary and potentially valuable tool for studying brain function by exposing relevant variation that is typically ignored.

The impact of alternating drainage and inundation cycles on geochemistry and microbiology of intact peat cores.

The rewetting of degraded peatlands has been adopted as a method to address climate change. Concerns have been raised about the effects of peat inundation and drying cycles, in more extreme climate events, on the potential release of nitrogen (N) species, in particular ammonium (NH4-N), once rewetted, as well as the physico-chemical and biological properties of the peat. This study used intact peat cores to measure the impact of two different cycles of peat inundation and drying (1 month and 2 month) over a total study duration of 56 weeks on the (1) NH4-N, nitrate-N (NO3-N) and dissolved reactive phosphorus (DRP) in the soil pore water; (2) microbial community structure; (3) physico-chemical properties of the peat; and (4) the structure of the peat, and therefore its ability to mitigate flood risks and storm surges. The study found that rewetted cores released NO3-N in the pore water up to a concentration of 6.25 mg L-1, but had no appreciable impact on NH4-N, which remained below 1.7 mg L-1 over the study duration. DRP moved quickly though the upper layers of the cores, but physico-chemical analysis suggested it was adsorbed to more iron-rich soil, which was present at depths below 0.4 m in the cores. Time intervals between inundation produced no significant difference on the forms of inorganic N released, nor did it compact the soil or change the microbial community structure. The depth of the water table, however, had a significant impact on inorganic N release, particularly NO3-N, which indicates that this N species, and not NH4-N, may be problematic in rewetted peatlands.

Autophagy induced by taurolidine protects against polymicrobial sepsis by promoting both host resistance and disease tolerance.

Sepsis, septic shock, and their sequelae are the leading causes of death in intensive care units, with limited therapeutic options. Disease resistance and tolerance are two evolutionarily conserved yet distinct defense strategies that protect the host against microbial infection. Here, we report that taurolidine administered at 6 h before septic challenge led to strong protection against polymicrobial sepsis by promoting both host resistance and disease tolerance characterized by accelerated bacterial clearance, ameliorated organ damage, and diminished vascular and gut permeability. Notably, taurolidine administered at 6 h after septic challenge also rescued mice from sepsis-associated lethality by enhancing disease tolerance to tissue and organ injury. Importantly, this in vivo protection afforded by taurolidine depends on an intact autophagy pathway, as taurolidine protected wild-type mice but was unable to rescue autophagy-deficient mice from microbial sepsis. In vitro, taurolidine induced light chain 3-associated phagocytosis in innate phagocytes and autophagy in vascular endothelium and gut epithelium, resulting in augmented bactericidal activity and enhanced cellular tolerance to endotoxin-induced damage in these cells. These results illustrate that taurolidine-induced autophagy augments both host resistance and disease tolerance to bacterial infection, thereby conferring protection against microbial sepsis.

Primary hyperparathyroidism causing posterior reversible encephalopathy syndrome: a case report.

Posterior reversible encephalopathy syndrome (PRES) is a reversible leukoencephalopathy characterised by subcortical vasogenic oedema and neurological signs. We present the case of a 64-year-old woman who presented to hospital with symptomatic primary hyperparathyroidism. Her parathyroid hormone (PTH) level on admission was elevated at 1,330ng/l (normal range15-68ng/l) and her serum calcium measured 4.83mmol/l (normal range 2.25-2.54mmol/l). Technectium-99m sestamibi scan demonstrated a focus of radiotracer uptake consistent with a right upper parathyroid adenoma or carcinoma. After commencing appropriate medical treatment, the patient developed intractable seizures necessitating endotracheal intubation. Magnetic resonance imaging of her brain revealed bilateral symmetrical T2 hyperintensities in the posterior circulation consistent with PRES. Following stabilisation and further medical treatment for hypercalcaemia, the patient underwent a parathyroidectomy. Preoperative rapid PTH assay measured 1,021ng/l. Following excision, PTH levels fell to just 10ng/l. She was extubated in the intensive care unit on postoperative day 1 and made an uneventful recovery. At her 6-week follow-up appointment, all neurological symptoms had resolved. PRES is a rare neurological entity more often seen in the setting of hypertension, immunosuppression and renal failure. The development of new neurological manifestations in the setting of known risk factors should raise suspicion for the underlying diagnosis.

Evaluation of the Cytotoxic Effects of the Novel Antineoplastic Agent 1,4,5-Oxathiazinane-4,4-dioxide on Triple Negative Breast Cancer Cells.

BACKGROUND/AIM: Adjuvant therapeutic options are limited for triple negative breast cancer (TNBC). Thus, we evaluated the cytotoxic effects of the newly synthesized antineoplastic agent 1,4,5-Oxathiazinane-4,4-dioxide (OTD) on TNBC cells as a potential cancer therapeutic strategy. MATERIALS AND METHODS: TNBC primary BT-20 and metastatic MDA-MB-231 cell lines were treated with increasing concentrations of OTD for various time periods to assess cell viability. Cell necrosis, apoptosis, necroptosis, autophagy, and ROS generation were evaluated using assay kits or specific inhibitors. RESULTS: Treatment with OTD resulted in a dose- and time-dependent cell death of TNBC BT-20 and MDA-MB-231 cells. OTD also dose-dependently arrested TNBC cell proliferation. Notably, treatment with OTD induced both necrosis and apoptosis of TNBC cells, while the pan-caspase inhibitor Z-VAD-FMK partially attenuated OTD-induced cell death. Importantly, abrogated OTD-induced cell death was observed in the presence of the ROS scavenger N-acetylcysteine (NAC), whereas enhanced OTD-induced cell death was observed after the addition of the glutathione synthesis inhibitor BSO, indicating OTD-induced killing of TNBC cells via a reactive oxygen species-dependent mechanism. CONCLUSION: OTD is strongly cytotoxic to both primary and metastatic TNBC cells, possibly by inducing multiple cell death pathways.

Screening for second malignancies in mycosis fungoides: non-Hodgkin lymphoma, Hodgkin lymphoma, lung cancer, bladder cancer and melanoma.

BACKGROUND: Patients with mycosis fungoides (MF) are at increased risk of developing non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), lung cancer, bladder cancer and melanoma. The characteristics of patients developing these malignancies have not been specifically delineated. In addition, there are no established guidelines for screening MF patients for second malignancies. MATERIALS/METHODS: We identified 742 patients with MF who developed second malignancies in the Surveillance Epidemiology and End Result-18 database. RESULTS: The majority of second malignancy patients were white and male, mean age 55-67 years at diagnosis of MF, and mean age 61-72 years at diagnosis of second malignancy. The majority of patients diagnosed with second malignancies had early stage MF. MF patients with NHL, lung cancer, and bladder cancer tended to be diagnosed at earlier stages of the second malignancy than patients without MF and demonstrated better 5-year overall survival. There was no improvement in stage at diagnosis or survival for MF patients who were diagnosed with melanoma compared to patients without MF. CONCLUSIONS: Improvements in survival in MF/NHL, MF/lung cancer and MF/bladder cancer patients may reflect differences in disease biology secondary to having MF or the importance of increased contact with the healthcare system. MF/melanoma data suggest that patients require regular pigmented-lesion-focused skin examinations. Tools for screening include regular lymph node examinations, pigmented-lesion-focused examinations and detailed review of systems questions. Smoking cessation counseling is key intervention in this population, as is ensuring that all age- and sex-specific cancer screenings are up-to-date (e.g. lung cancer screening, mammography, and colonoscopy). The utility of regular imaging for second malignancy screening and lab testing such as routine urinalysis requires additional study and expert consensus.

A Randomized Clinical Trial Evaluating the Efficacy and Quality of Life of Antibiotic-only Treatment of Acute Uncomplicated Appendicitis: Results of the COMMA Trial.

OBJECTIVE: Evaluate the efficacy and quality of life associated with conservative treatment of acute uncomplicated appendicitis. SUMMARY BACKGROUND DATA: Conservative management with antibiotics only has emerged as a potential treatment option for acute uncomplicated appendicitis. However the reported failure rates are highly variable and there is a paucity of data in relation to quality of life. METHODS: Symptomatic patients with radiological evidence of acute, uncomplicated appendicitis were randomized to either intravenous antibiotics only or undergo appendectomy. RESULTS: One hundred eighty-six patients underwent randomization. In the antibiotic-only group, 23 patients (25.3%) experienced a recurrence within 1 year following randomization. There was a significantly better EQ-VAS quality of life score in the surgery group compared with the antibiotic-only group at 3 months (94.3 vs 91.0, P < 0.001) and 12 months postintervention (94.5 vs 90.4, P < 0.001). The EQ-5D-3L quality-of-life score was significantly higher in the surgery group indicating a better quality of life (0.976 vs 0.888, P < 0.001). The accumulated 12-month sickness days was 3.6 days shorter for the antibiotics only group (5.3 vs 8.9 days; P < 0.01). The mean length of stay in both groups was not significantly different (2.3 vs 2.8 days, P = 0.13). The mean total cost in the surgery group was significantly higher than antibiotics only group (€4,816 vs €3,077, P < 0.001). CONCLUSIONS: Patients with acute, uncomplicated appendicitis treated with antibiotics only experience high recurrence rates and an inferior quality of life. Surgery should remain the mainstay of treatment for this commonly encountered acute surgical condition.

Preoperative assessment of skeletal muscle mass during magnetic resonance enterography in patients with Crohn's disease.

Measurement of the psoas muscle area has been applied to estimate lean muscle mass as a surrogate marker of sarcopenia, but there is a paucity of evidence regarding the influence of sarcopenia on clinical outcomes following inflammatory bowel disease surgery. The aim of this study was to evaluate the association between MRI enterography defined sarcopenia and postoperative complications in patients undergoing elective ileocaecal resection for Crohn's disease. To obtain cross sectional area measurement of the psoas muscle, the freehand area tool was used to trace the margin of each psoas muscle at the level of L4, with the sum recorded as Total Psoas Area (TPA). The total cross sectional muscle area of the abdominal wall was recorded as Skeletal Muscle Area (SMA), while myosteatosis was measured by normalising the psoas muscle intensity with the mean intensity of the cerebrospinal fluid. The primary outcome was the incidence of 30-day postoperative complications in patients in the lowest quartile of TPA and SMA. 31 patients were included and ten patients (32.25%) developed postoperative complications within 30 days of surgery. The cut-off values for the lowest quartile for TPA were 11.93 cm2 in men and 9.77 cm2 in women, including a total of 8 patients (25.8%) with 5 patients in this group (62.5%) developing postoperative complications and 3 patients (37.5%) Clavien-Dindo class ≥ 3 complications. The cut-off values for the lowest quartile for SMA were 73.49 cm2 in men and 65.85 cm2 in women, with 4 patients out of 8 (50%) developing postoperative complications. Psoas muscle cross sectional area and skeletal mass area can be estimated on Magnetic Resonance Enterography as surrogate markers of sarcopenia with high inter-observer agreement.

The impact of COVID-19 upon student radiographers and clinical training.

INTRODUCTION: To investigate student clinical placement concerns and opinions, during the initial COVID-19 pandemic outbreak and to inform educational institution support planning. METHODS: Between mid-June to mid-July 2020, educational institutions from 12 countries were invited to participate in an online survey designed to gain student radiographer opinion from a wide geographical spread and countries with varying levels of COVID-19 cases. RESULTS: 1277 respondents participated, of these 592 had completed clinical placements during January to June 2020. Accommodation and cohabiting risks were identified as challenging, as was isolation from family, travel to clinical placements, and to a lesser extent childcare. Students stated they had been affected by the feeling of isolation and concerns about the virus whilst on placement. Overall 35.4% of all respondents were 'Not at all worried' about being a radiographer, however, 64.6% expressed varying levels of concern and individual domestic or health situations significantly impacted responses (p ≤ 0.05). Year 4 students and recent graduates were significantly more likely to be 'Not worried at all' compared to Year 2 and 3 students (p ≤ 0.05). The need for improved communication regarding clinical placements scheduling was identified as almost 50% of students on clinical placements between January to June 2020 identified the completion of assessments as challenging. Furthermore, only 66% of respondents with COVID-19 imaging experience stated being confident with personal protective equipment (PPE) use. CONCLUSION: Student radiographers identified key challenges which require consideration to ensure appropriate measures are in place to support their ongoing needs. Importantly PPE training is required before placement regardless of prior COVID-19 imaging experience. IMPLICATIONS FOR PRACTICE: As the next academic year commences, the study findings identify important matters to be considered by education institutions with responsibility for Radiography training and as students commence clinical placements during the on-going global COVID-19 pandemic.

Role of circulating fibrocytes in the diagnosis of acute appendicitis.

BACKGROUND: Improved diagnostic biomarkers are required for acute appendicitis. The circulating fibrocyte percentage (CFP) is increased in inflammatory states, but has not been studied in acute appendicitis. This study aimed to determine CFP in acute appendicitis and compare diagnostic accuracy with standard serological biomarkers. METHODS: A prospective cohort study was carried out between June 2015 and February 2016 at University Hospital Limerick. The CFP was determined by dual-staining peripheral venous samples for CD45 and collagen I using fluorescence-activated cell sorting, and correlated with histopathological diagnoses. The accuracy of CFP in determining histological acute appendicitis was characterized and compared with the white cell count, C-reactive protein concentration, neutrophil count, lymphocyte count and neutrophil : lymphocyte ratio. RESULTS: Of 95 adults recruited, 15 were healthy individuals and 80 had suspected appendicitis at presentation. Forty-six of these 80 patients had an appendicectomy, of whom 34 had histologically confirmed appendicitis. The CFP was statistically higher in patients with pathologically proven acute appendicitis than in healthy controls (median 6·1 (i.q.r. 1·6-11·6) versus 2·3 (0·9-3·4) per cent respectively; P = 0·008). The diagnostic accuracy of CFP, as determined using the area under the receiver operating characteristic (ROC) curve, was similar to that of standard biomarkers. In multinomial regression analysis, only raised CFP was retained as an independent prognostic determinant of acute appendicitis (odds ratio 1·57, 95 per cent c.i. 1·05 to 2·33; P = 0·027). CONCLUSION: The CFP is increased in histologically confirmed acute appendicitis and is as accurate as standard serological biomarkers in terms of diagnosis.

Mycosis fungoides: developments in incidence, treatment and survival.

BACKGROUND: Prior studies have demonstrated improved disease-specific survival of mycosis fungoides (MF) patients over the last 50 years. OBJECTIVE: To analyse patterns of survival and incidence from 1973 to 2016 and determine whether apparent improvements in MF-specific survival are due to lead-time bias rather than improvements in treatment. METHODS: We performed an analysis of 10 155 patients diagnosed with MF from 1973 to 2016 in the United States cancer registries of SEER-18. We also performed a literature review of papers including stage data for unselected populations of MF patients prior to 2000. RESULTS: Incidence of MF increased from 3.0 per million person-years in the 1970s to 5.9 in the 2010s. For all cohorts, non-Hodgkin lymphoma (including MF) was the leading cause of death. Survival analysis demonstrated marked improvement in disease-specific and overall survival from the 1970s to 2010s. Based on systematic review of the literature, 32%-73% of patients diagnosed prior to 2000 were diagnosed with early-stage disease, as opposed to 81% of patients in the SEER 2000-2016 cohort (P < 0.035 for all cohorts). CONCLUSIONS: Although there have been improvements in MF-related survival over the last 50 years, these may reflect improvements in our ability to diagnose early-stage disease rather than improved treatment.

Juvenile systemic lupus erythematosus presenting as pancarditis.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with marked variation in its clinical presentation. Juvenile SLE (jSLE) accounts for 15-20% of all cases and is diagnosed when SLE manifests before 18 years of age. Pancarditis is a rare complication of SLE, regardless of age of disease onset. CASE PRESENTATION: We report a case of jSLE in a 15 year old Caucasian female presenting with an acute episode of pancarditis and multiorgan dysfunction who was successfully treated with systemic corticosteroids and cyclophosphamide. CONCLUSION: Pancarditis can be a presenting feature of jSLE which was previously unreported. A high index of suspicion for severe cardiac involvement is required at all stages of disease.

Longer small bowel segments are resected in emergency surgery for ileocaecal Crohn's disease with a higher ileostomy and complication rate.

BACKGROUND: Repeated intestinal resections may have disabling consequences in patients with Crohn's disease even in the absence of short bowel syndrome. Our aim was to evaluate the length of resected small bowel in patients undergoing elective and emergency surgery for ileocolic Crohn's disease. METHODS: A prospective observational study was conducted on patients undergoing surgery for ileocolonic Crohn's disease in a single colorectal centre from May 2010 to April 2018. The following patients were included: (1) patients with first presentation of ileocaecal Crohn's disease undergoing elective surgery; (2) patients with ileocaecal Crohn's disease undergoing emergency surgery; (3) patients with recurrent Crohn's disease of the distal ileum undergoing elective surgery. The primary outcomes were length of resected small bowel and the ileostomy rate. Operating time, complications and readmissions within 30 days were the secondary outcomes. RESULTS: One hundred and sixty-eight patients were included: 87 patients in the elective primary surgery group, 50 patients in the emergency surgery group and 31 in the elective redo surgery group. Eleven patients (22%) in the emergency surgery group had an ileostomy compared to 10 (11.5%) in the elective surgery group (p < 0.0001). In the emergency surgery group the median length of the resected small bowel was 10 cm longer than into the group having elective surgery for primary Crohn's disease. CONCLUSIONS: Patients undergoing emergency surgery for Crohn's disease have a higher rate of stoma formation and 30-day complications. Laparoscopic surgery in the emergency setting has a higher conversion rate and involves resection of longer segments of small bowel.

Nuclear singlet relaxation by scalar relaxation of the second kind in the slow-fluctuation regime.

The singlet state of nuclear spin-1/2 pairs is protected against many common relaxation mechanisms. Singlet order, which is defined as the population difference between the nuclear singlet and triplet states, usually decays more slowly than the nuclear magnetization. Nevertheless, some decay mechanisms for nuclear singlet order persist. One such mechanism is called scalar relaxation of the second kind (SR2K) and involves the relaxation of additional nuclei ("third spins") which have scalar couplings to the spin-1/2 pair. This mechanism requires a difference between the couplings of at least one third spin with the two members of the spin-1/2 pair, and depends on the longitudinal relaxation time of the third spin. The SR2K mechanism of nuclear singlet relaxation has previously been examined in the case where the relaxation rate of the additional spins is on the time scale of the nuclear Larmor frequency. In this paper, we consider a different regime, in which the longitudinal relaxation of the third spins is on a similar time scale to the J-coupling between the members of the spin pair. This regime is often encountered when the spin-1/2 pair has scalar couplings to nearby deuterium nuclei. We show that the SR2K mechanism may be suppressed in this regime by applying a radiofrequency field which is resonant either with the members of the spin pair, or with the third spins. These phenomena are analyzed theoretically and by numerical simulations, and demonstrated experimentally on a diester of [13C2, 2H2]-labeled fumarate in solution.

RandomiSed clinical trial assessing Use of an anti-inflammatoRy aGent in attenUating peri-operatiVe inflAmmatioN in non-meTastatic colon cancer - the S.U.R.G.U.V.A.N.T. trial.

BACKGROUND: Peri-operative inflammation has been extensively highlighted in cancer patients as detrimental. Treatment strategies to improve survival for cancer patients through targeting peri-operative inflammation have yet to be devised. METHODS: We conducted a multi-centre, randomised controlled clinical trial using Taurolidine in non-metastatic colon cancer patients. Patients were randomly assigned to receive Taurolidine or a placebo. The primary endpoint for the study was the mean difference in day 1 IL-6 levels. Secondary clinical endpoints included rates of post-operative infections and tumor recurrence. RESULTS: A total of 293 patients were screened for trial inclusion. Sixty patients were randomised. Twenty-eight patients were randomised to placebo and 32 patients to Taurolidine. IL-6 levels were equivalent on day 1 post-operatively in both groups. However, IL-6 levels were significantly attenuated over the 7 day study period in the Taurolidine group compared to placebo (p = 0.04). In addition, IL-6 levels were significantly lower at day 7 in the Taurolidine group (p = 0.04). There were 2 recurrences in the placebo group at 2 years and 1 in the Taurolidine group. The median time to recurrence was 19 months in the Placebo group and 38 months in the Taurolidine group (p = 0.27). Surgical site infection was reduced in the Taurolidine treated group (p = 0.09). CONCLUSION: Peri-operative use of Taurolidine significantly attenuated circulating IL-6 levels in the initial 7 day post-operative period in a safe manner. Future studies are required to establish the impact of IL-6 attenuation on survival outcomes in colon cancer. TRIAL REGISTRATION: The trial was registered with EudraCT (year = 2008, registration number = 005570-12 ) and ISRCTN (year = 2008, registration number = 77,829,558 ).

Recent advances in ruthenium-based olefin metathesis.

Ruthenium-based olefin metathesis catalysts, known for their functional group tolerance and broad applicability in organic synthesis and polymer science, continue to evolve as an enabling technology in these areas. A discussion of recent mechanistic investigations is followed by an overview of selected applications.

Resting-state thalamic dysconnectivity in schizophrenia and relationships with symptoms.

BACKGROUND: Schizophrenia (SZ) is a severe neuropsychiatric disorder associated with disrupted connectivity within the thalamic-cortico-cerebellar network. Resting-state functional connectivity studies have reported thalamic hypoconnectivity with the cerebellum and prefrontal cortex as well as thalamic hyperconnectivity with sensory cortical regions in SZ patients compared with healthy comparison participants (HCs). However, fundamental questions remain regarding the clinical significance of these connectivity abnormalities. METHOD: Resting state seed-based functional connectivity was used to investigate thalamus to whole brain connectivity using multi-site data including 183 SZ patients and 178 matched HCs. Statistical significance was based on a voxel-level FWE-corrected height threshold of p < 0.001. The relationships between positive and negative symptoms of SZ and regions of the brain demonstrating group differences in thalamic connectivity were examined. RESULTS: HC and SZ participants both demonstrated widespread positive connectivity between the thalamus and cortical regions. Compared with HCs, SZ patients had reduced thalamic connectivity with bilateral cerebellum and anterior cingulate cortex. In contrast, SZ patients had greater thalamic connectivity with multiple sensory-motor regions, including bilateral pre- and post-central gyrus, middle/inferior occipital gyrus, and middle/superior temporal gyrus. Thalamus to middle temporal gyrus connectivity was positively correlated with hallucinations and delusions, while thalamus to cerebellar connectivity was negatively correlated with delusions and bizarre behavior. CONCLUSIONS: Thalamic hyperconnectivity with sensory regions and hypoconnectivity with cerebellar regions in combination with their relationship to clinical features of SZ suggest that thalamic dysconnectivity may be a core neurobiological feature of SZ that underpins positive symptoms.