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1.
Clin Obes ; 14(3): e12650, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38425267

ABSTRACT

Enhanced recovery after surgery (ERAS) protocols are shown to improve patient outcomes and reduce length of hospital stay. However, there is currently limited consensus on the perioperative management of patients undergoing bariatric and metabolic surgery (BMS) in the United Kingdom. This study aims to survey the level of consistency in patient care undergoing BMS. Bariatric nurse specialists from 30 bariatric units completed an anonymised, online survey from 21 December 2022 to 21 February 2023. Most units (77%) have implemented a premade postoperative care bundle protocol including predetermined timing of oral intake (77%) and postoperative day 1 bloods (60%). 63% of units have also established pre-set analgesia and anti-emetic bundles. Date of discharge is variable, ranging from 1 day after surgery (50%) to a 'two night stay' protocol (33%) to within 4 days after surgery (17%). Most follow-up clinics are either led by dietitians (33%) or both bariatric nurse specialists and dietitians collaboratively (57%). Patients are usually established on solid food 6 weeks after surgery in 53% (16/30) units. Chemical venous thromboembolism (VTE) prophylaxis was either given on day of surgery postoperatively (60%), day before (20%) or after (17%) surgery. Our study shows significant variability of care throughout the surgical pathway, in the study population. The results suggest a need for consensus guidelines outlining the best-practice approach to managing patients undergoing BMS; due to the heterogeneity of the patient group, these guidelines should contain overarching generalisable recommendations that can then be tailored to individual patients.


Subject(s)
Bariatric Surgery , Perioperative Care , Humans , United Kingdom , Perioperative Care/standards , Perioperative Care/methods , Enhanced Recovery After Surgery/standards , Length of Stay/statistics & numerical data , Obesity, Morbid/surgery , Surveys and Questionnaires , Female
2.
Res Sq ; 2023 Jul 03.
Article in English | MEDLINE | ID: mdl-37461513

ABSTRACT

Maternal infections during pregnancy pose an increased risk for neurodevelopmental psychiatric disorders (NPDs) in the offspring. Here, we examined age- and sex-dependent dynamic changes of the hippocampal synaptic proteome after maternal immune activation (MIA) in embryonic and adult mice. Adult male and female MIA offspring exhibited social deficits and sex-specific depression-like behaviours, among others, validating the model. Furthermore, we observed dose-, age-, and sex-dependent synaptic proteome differences. Analysis of the embryonic synaptic proteome implicates sphingolipid and ketoacid metabolism pathway disruptions during neurodevelopment for NPD-pertinent sequelae. In the embryonic hippocampus, prenatal immune activation also led to changes in neuronal guidance, glycosphingolipid metabolism important for signalling and myelination, and post-translational modification of proteins that regulate intercellular interaction and developmental timing. In adulthood, the observed changes in synaptoneurosomes revealed a dynamic shift toward transmembrane trafficking, intracellular signalling cascades, and hormone-mediated metabolism. Importantly, 68 of the proteins with differential abundance in the embryonic brains of MIA offspring were also altered in adulthood, 75% of which retained their directionality. These proteins are involved in synaptic organisation, neurotransmitter receptor regulation, and the vesicle cycle. A cluster of persistently upregulated proteins, including AKT3, PAK1/3, PPP3CA, formed a functional network enriched in the embryonic brain that is involved in cellular responses to environmental stimuli. To infer a link between the overlapping protein alterations and cognitive and psychiatric traits, we probed human phenome-wise association study data for cognitive and psychiatric phenotypes and all, but PORCN were significantly associated with the investigated domains. Our data provide insights into the dynamic effects of an early prenatal immune activation on developing and mature hippocampi and highlights targets for early intervention in individuals exposed to such immune challenges.

3.
Obes Surg ; 33(6): 1866-1875, 2023 06.
Article in English | MEDLINE | ID: mdl-37067684

ABSTRACT

This study aims to be a contemporary review of mHealth apps in bariatric and metabolic surgery (BMS) to assess their quality using the Silberg scale as well as features, themes, usability, and medical/allied health professional involvement (MAPI). Apps were identified using search terms in the Android and Apple app stores. 52 apps were included. 42 (80.7%) apps main target users were patients. More than half, 27 (52%), targeted US based users. 29 (56%) had payment-restricted content. 42 (81%) had MAPI and the mean Silberg score was 5.2. Compared to previous studies the quality of BMS apps is improving with more MAPI and useful functionality. Wider use of mHealth apps for patient centred follow-up, management and care are yet to be widely implemented and explored.


Subject(s)
Bariatric Surgery , Mobile Applications , Obesity, Morbid , Telemedicine , Humans , Smartphone , Obesity, Morbid/surgery
4.
World J Surg ; 47(6): 1348-1357, 2023 06.
Article in English | MEDLINE | ID: mdl-36811667

ABSTRACT

BACKGROUND: The ward round is an integral part of everyday surgical practice. It is a complex clinical activity that requires both sound clinical management and communication skills. This study reports the results of a consensus-building exercise on the common aspects of the general surgical ward rounds. METHODS: The consensus-building committee involving a range of stakeholders from 16 United Kingdom (UK) National Health Service trusts took part in this consensus exercise. The members discussed and suggested a series of statements concerning surgical ward round. An agreement of ≥ 70% among members was regarded as a consensus. RESULTS: Thirty-two members voted on 60 statements. There was a consensus on fifty-nine statements after the first round of voting, and one statement was modified before it reached consensus in the second round. The statements covered nine sections: a preparation phase, team allocation, multidisciplinary approach to the ward round, structure of the round, teaching considerations, confidentiality and privacy, documentation, post-round arrangements, and weekend round. There was a consensus on spending time to prepare for the round, a consultant-led round, involvement of the nursing staff, an MDT round at the beginning and end of the week, a minimum of 5 min allocated to each patient, utilisation of a round checklist, afternoon virtual round, and a clear handover and plan for the weekend. CONCLUSION: The consensus committee achieved agreement on several aspects concerning the surgical ward rounds in the UK NHS. This should help improve the care of surgical patients in the UK.


Subject(s)
State Medicine , Humans , Consensus , Delphi Technique , United Kingdom
5.
Obes Surg ; 33(4): 1049-1059, 2023 04.
Article in English | MEDLINE | ID: mdl-36609742

ABSTRACT

INTRODUCTION: Internal herniation (IH) can be a life-threatening complication of Roux-en-Y gastric bypass (RYGB). Randomised controlled trials support the routine closure of mesenteric spaces at RYGB. However, there is currently no consensus on the method of closure in clinical practice. The purpose of this survey is to understand bariatric surgeons' practice in this regard. METHODS: We conducted an international survey, whereby questions were created through collaboration of a consensus group of bariatric surgeons and hosted on the SurveyMonkey platform. The survey was distributed among British Obesity and Metabolic Surgery Society (BOMSS) members and international professional channels including The Upper Gastrointestinal Society (TUGS) and social media. RESULTS: One hundred and thirty-six surgeons from 34 countries completed the survey. Of these, 49 respondents were UK-based surgeons with a cumulative experience of approximately 2500 RYGB per annum. Forty-five (91.8%) respondents reported always closing mesenteric defects, of whom 57.8% elected to use non-absorbable non-barbed sutures, followed by staples/clips in 28.9% and a selection of other methods. Most respondents used more than one method. A total of 2 UK and 14 non-UK participants reported never closing mesenteric spaces. CONCLUSIONS: This survey has shown heterogeneity among defect closure and no consensus on preferred type. Additionally, there remains a practice of non-closure of mesenteric defects. We hope these findings help to inform further needed research and consensus building among experts.


Subject(s)
Gastric Bypass , Hernia, Abdominal , Laparoscopy , Obesity, Morbid , Humans , Gastric Bypass/adverse effects , Obesity, Morbid/surgery , Laparoscopy/adverse effects , Hernia/complications , Obesity/surgery , Postoperative Complications/etiology , Retrospective Studies , Hernia, Abdominal/etiology
6.
Eur Neuropsychopharmacol ; 67: 66-79, 2023 02.
Article in English | MEDLINE | ID: mdl-36513018

ABSTRACT

The neuronal isoform of nitric oxide synthase (nNOS) and its interacting protein NOS1AP have been linked to several mental disorders including schizophrenia and depression. An increase in the interaction between nNOS and NOS1AP in the frontal cortex has been suggested to contribute to the emergence of these disorders. Here we aimed to uncover whether disruption of their interactions in the frontal cortex leads to mental disorder endophenotypes. Targeting the medial prefrontal cortex (mPFC), we stereotaxically injected wild-type C57BL/6J mice with recombinant adeno-associated virus (rAAV) expressing either full-length NOS1AP, the nNOS binding region of NOS1AP (i.e. NOS1AP396-503), or the nNOS amino-terminus (i.e. nNOS1-133), which was shown to disrupt the interaction of endogenous nNOS with PSD-95. We tested these mice in a comprehensive behavioural battery, assessing different endophenotypes related to mental disorders. We found no differences in anxiety-related and exploratory behaviours. Likewise, social interaction was comparable in all groups. However, social recognition was impaired in NOS1AP and NOS1AP396-503 mice. These mice, as well as mice overexpressing nNOS1-133 also displayed impaired spatial working memory (SWM) capacity, while spatial reference memory (SRM) remained intact. Finally, mice overexpressing NOS1AP and nNOS1-133, but not NOS1AP396-503, failed to habituate to the startling pulses in an acoustic startle response (ASR) paradigm, though we found no difference in overall startle intensity or prepulse inhibition (PPI) of the ASR. Our findings indicate a distinct role of NOS1AP/nNOS/PSD-95 interactions in the mPFC to contribute to specific endophenotypic changes observed in different mental disorders.


Subject(s)
Memory, Short-Term , Reflex, Startle , Mice , Animals , Mice, Inbred C57BL , Nitric Oxide Synthase Type I/genetics , Recognition, Psychology , Memory Disorders , Disks Large Homolog 4 Protein/metabolism , Prefrontal Cortex/metabolism , Adaptor Proteins, Signal Transducing/genetics
7.
J Surg Case Rep ; 2022(11): rjac465, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36381985

ABSTRACT

A 46-year-old female underwent elective laparoscopic hysterectomy. Seven days post-operatively, she presented with urinary leak from the vagina. Computed tomography urogram demonstrated a right complete ureteric transection with leakage of urine into the pelvis and fistulation into the vagina. A rendezvous procedure was performed via a retrograde cystoscopic approach during which a guidewire was used to cannulate the right ureteric orifice and coiled in the retroperitoneal cavity. Subsequently, via a right percutaneous nephrostomy, a guidewire was advanced through the site of ureteric transection, which was followed by a snare catheter to bring the retrograde wire externally. A nephroureteric stent was then inserted. Twelve weeks later, the nephroureteric stent was exchanged for a ureteric stent for 6 months. A subsequent retrograde ureterogram showed complete healing of the ureter. The ureteric stent was removed and follow-up ultrasounds revealed no hydronephrosis. Percutaneous rendezvous procedures represent an effective option to treat this challenging condition.

8.
Obes Surg ; 32(11): 3740-3751, 2022 11.
Article in English | MEDLINE | ID: mdl-36057021

ABSTRACT

Patient and public involvement (PPI) has gained increased attention in research circles. The consistency of PPI reporting has been addressed by the development of validated checklists such as GRIPP and GRIPP2. The primary aim of this study was to identify the incidence of PPI reporting in bariatric research. MEDLINE/PubMed, EMBASE, and CINAHL/Cochrane databases were searched for publications between 1st January 2018 to 31st December 2021 for "bariatric surgery" OR "weight loss surgery" OR "obesity surgery" AND "randomized controlled trials." Ninety studies fulfilled exclusion criteria; two studies reported direct PPI involvement, one indirectly used PPI and one reported not using PPI methods. No other study made direct or indirect mention of PPI. Concluding, that GRIPP2 and PPI reporting in bariatric surgery trials is lacking.


Subject(s)
Bariatric Surgery , Obesity, Morbid , Humans , Obesity, Morbid/surgery , Patient Participation , Checklist
9.
Obes Surg ; 32(11): 3627-3634, 2022 11.
Article in English | MEDLINE | ID: mdl-36057022

ABSTRACT

INTRODUCTION: The role of esophago-gastro-duodenoscopy (EGD) in bariatric surgery has been widely discussed. In 2020, the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) issued recommendations on the routine use of EGD before and after bariatric surgery. However, little is known of our current practice and the guidance uptake. METHODS: We conducted an international survey assessing bariatric surgeons' practice on the use of EGD. The survey aimed to identify whether surgeons offer EGD in the following settings: pre-operative, post-operative at 1 year, every 2-3 years following longitudinal sleeve gastrectomy (LSG) or one-anastomosis gastric bypass (OAGB). Data was analyzed using descriptive statistics. RESULTS: Among 121 respondents, 72% are aware of the IFSO recommendations. The commonly performed bariatric procedures were LSG, Roux-en-Y gastric bypass (RYGB), and OAGB. 53.7% surgeons routinely offer pre-operative EGD and 14.3% routinely offer post-operative EGD for bariatric patients at 1 year after surgery. Majority do not routinely offer EGD after LSG (74.8%) or OAGB (79.7%) every 2-3 years as proposed by IFSO. CONCLUSION: The uptake of IFSO recommendation is variable according to each recommendation with better compliance among surgeons with regard to pre-operative EGD. Further research is necessary to develop robust evidence-base for the role of endoscopy after bariatric surgery with the inclusion of patient and public involvement.


Subject(s)
Bariatric Surgery , Gastric Bypass , Obesity, Morbid , Humans , Obesity, Morbid/surgery , Duodenoscopy , Bariatric Surgery/methods , Gastric Bypass/methods , Gastrectomy/methods , Surveys and Questionnaires , Retrospective Studies
10.
Br J Radiol ; 95(1137): 20220024, 2022 Sep 01.
Article in English | MEDLINE | ID: mdl-35786972

ABSTRACT

OBJECTIVES: The advent of the COVID-19 pandemic has resulted in periods of nationwide restrictions in Ireland including school and workplace closures. The authors hypothesised that this disruption to society may have led to a change in patterns of suspected physical abuse (SPA) presentations to the paediatric emergency department (ED), whilst ED attendance fell dramatically during the period. We reviewed data to determine whether there was an increase in presentations of SPA during periods of social restrictions. METHODS: The National Integrated Medical Imaging Service was searched for all skeletal survey examinations performed between the dates of the 1 March 2016 and 28 Feb 2021 for studies performed in cases of SPA. Electronic records of attendance were extracted from the emergency department administrative system at the three paediatric emergency departments which serve the 400,000 children regionally. The data were reviewed to determine if SPA presentations increased during restriction periods. RESULTS: 311 individual paediatric patients aged 24 months and under were referred for SPA skeletal survey during the study period. During the 2020/2021 period, 60 children were referred for SPA workup and there was no statistically significant difference between monthly referrals (mean 5, sd 2.92) in this period and matched periods over the preceding 4 years (mean 5.23, sd 2.69). CONCLUSIONS: The incidence of SPA did not increase during the period of national restrictions during the COVID-19 pandemic. ADVANCES IN KNOWLEDGE: Periods of social restrictions taken to protect the public health during a pandemic do not result in short term increases in suspected physical abuse in the regional paediatric population.


Subject(s)
COVID-19 , Pandemics , COVID-19/epidemiology , Child , Cross-Sectional Studies , Emergency Service, Hospital , Humans , Incidence , Multicenter Studies as Topic , Physical Abuse , Retrospective Studies
11.
Ir J Med Sci ; 191(5): 2041-2046, 2022 Oct.
Article in English | MEDLINE | ID: mdl-34727342

ABSTRACT

The Sentry bioconvertible IVC filter (Boston Scientific, MA, USA) contains a bioabsorbable filament which hydrolyses after 60 days, allowing the arms of the filter to spring open, retract into the vessel wall and endothelialise, leaving an unobstructed IVC lumen.It is a novel treatment option for patients at transient risk of pulmonary emboli with a contraindication to anticoagulation. The device provides similar protection to other currently available devices against pulmonary emboli with minimal complications. It represents an effective alternative to retrievable filters, the removal of which is variously not attempted, not possible or associated with high complication rates.We review the literature which underpins the development of the bioconvertible filter. We describe our first deployment of the filter in an 85-year-old female with gastric malignancy (who subsequently underwent a subtotal gastrectomy) with a history of anaemia and previous pulmonary emboli. The availability of a bioconvertible filter constitutes a further step forward in the management of patients with potential or active thromboembolic disease.


Subject(s)
Pulmonary Embolism , Thromboembolism , Vena Cava Filters , Venous Thrombosis , Aged, 80 and over , Anticoagulants , Device Removal , Female , Humans , Pulmonary Embolism/prevention & control , Retrospective Studies , Thromboembolism/complications , Treatment Outcome , Vena Cava Filters/adverse effects
12.
Int J Surg Case Rep ; 85: 106277, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34388907

ABSTRACT

INTRODUCTION: Delayed upper gastrointestinal (GI) bleeding is a rare complication of esophagectomy and can be difficult to manage. PRESENTATION: A 76-year-old female represented 17 days post open esophagectomy with an unstable upper GI bleed. When control could not be achieved endoscopically, she was transferred to the Radiology Department where a triphasic CT angiogram confirmed active contrast extravasation into the gastric tube. She proceeded to the Interventional Radiology suite where a thoracic angiogram revealed an active arterial bleed from a branch of the thyrocervical trunk. The bleeding vessel was successfully embolised with coils and haemostasis was achieved. DISCUSSION: Management options for upper GI bleeding post esophagectomy include medical, endoscopic and endovascular approaches. CONCLUSION: Our case represents a rare example of delayed bleeding into a gastric conduit post open esophagectomy for a benign stricture. The case reinforces.

13.
EBioMedicine ; 71: 103565, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34455393

ABSTRACT

BACKGROUND: Nitric oxide synthase 1 adaptor protein (NOS1AP; previously named CAPON) is linked to the glutamatergic postsynaptic density through interaction with neuronal nitric oxide synthase (nNOS). NOS1AP and its interaction with nNOS have been associated with several mental disorders. Despite the high levels of NOS1AP expression in the hippocampus and the relevance of this brain region in glutamatergic signalling as well as mental disorders, a potential role of hippocampal NOS1AP in the pathophysiology of these disorders has not been investigated yet. METHODS: To uncover the function of NOS1AP in hippocampus, we made use of recombinant adeno-associated viruses to overexpress murine full-length NOS1AP or the NOS1AP carboxyterminus in the hippocampus of mice. We investigated these mice for changes in gene expression, neuronal morphology, and relevant behavioural phenotypes. FINDINGS: We found that hippocampal overexpression of NOS1AP markedly increased the interaction of nNOS with PSD-95, reduced dendritic spine density, and changed dendritic spine morphology at CA1 synapses. At the behavioural level, we observed an impairment in social memory and decreased spatial working memory capacity. INTERPRETATION: Our data provide a mechanistic explanation for a highly selective and specific contribution of hippocampal NOS1AP and its interaction with the glutamatergic postsynaptic density to cross-disorder pathophysiology. Our findings allude to therapeutic relevance due to the druggability of this molecule. FUNDING: This study was funded in part by the DFG, the BMBF, the Academy of Finland, the NIH, the Japanese Society of Clinical Neuropsychopharmacology, the Ministry of Education of the Russian Federation, and the European Community.


Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Endophenotypes , Gene Expression , Hippocampus/metabolism , Mental Disorders/etiology , Mental Disorders/metabolism , Adaptor Proteins, Signal Transducing/metabolism , Animals , Biomarkers , Disease Models, Animal , Disease Susceptibility , Disks Large Homolog 4 Protein/metabolism , Gene Expression Regulation , Hippocampus/physiopathology , Male , Mental Disorders/diagnosis , Mice , Nitric Oxide Synthase Type I/metabolism , Protein Binding , Signal Transduction
14.
Acta Radiol Open ; 10(2): 2058460120981001, 2021 Feb.
Article in English | MEDLINE | ID: mdl-33628459

ABSTRACT

Prostate cancer is the most common malignancy in men with high incidence of recurrence following treatment. Biochemical recurrence, as indicated by rising PSA levels following successful treatment of the primary disease, is a frequent encounter in routine clinical practice. 68Gallium-PSMA positron emission tomography/computer tomography has been widely accepted as the modality of choice with the highest impact in management of this group of patients. Pitfalls of this diagnostic technique stem from the diversity of histological entities, other than prostate tumour cells, which can demonstrate increased uptake of the radiotracer. We present a case of intracranial uptake of PSMA by meningioma in a patient with BCR, as a pitfall in imaging of prostate cancer. Knowledge of normal distribution of the tracer is of utmost importance when reading positron emission tomography/computer tomography imaging especially given the relative novelty of usage of 68Gallium-PSMA.

16.
Obes Surg ; 31(4): 1449-1454, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33405182

ABSTRACT

INTRODUCTION: One anastomosis gastric bypass (OAGB) offers favourable weight loss outcomes and is associated with reduced morbidity and mortality when compared to other mainstream bariatric procedures. However, a randomised trial reported a conversion rate to roux-en-Y configuration (RYC) of 3.1%, and some surgeons consider the procedure unsuitable for patients with a preoperative hiatus hernia (HH) or symptoms of gastrooesophageal reflux disease (GORD). METHODS: We carried out a retrospective review of patients undergoing OAGB in our institution. Included were all patients on PPI for symptoms of GORD preoperatively, as well as patients with HH or oesophagitis on preoperative endoscopy. We recorded GORD outcomes as well as rates of conversion to RYC in patients. RESULTS: Medium term follow up data at 23-28 months was available for 89 patients. Of these, 63 had HH, 34 had preoperative GORD requiring PPI and 9 had confirmed oesophagitis. The conversion rate to RYC was nil (0/63) in patients with HH. At the same time, 14.7% (5/34) of patients with preop GORD on PPI required conversion to RYC at a median time interval of 16 months. In patients already on PPI preoperatively, 16/34 (47.1%) needed to continue on PPI long term. In patients with HH, 20.6% (13/63) suffered de novo GORD symptoms. CONCLUSION: OAGB can be offered to patients with HH with acceptable GORD outcomes but caution is advised in patients with preoperative GORD symptoms. Larger prospective and randomised studies are required to further assess this subgroup.


Subject(s)
Gastric Bypass , Gastroesophageal Reflux , Hernia, Hiatal , Obesity, Morbid , Gastroesophageal Reflux/surgery , Hernia, Hiatal/surgery , Humans , Obesity, Morbid/surgery , Prospective Studies , Retrospective Studies
17.
Acta Radiol ; 62(2): 276-280, 2021 Feb.
Article in English | MEDLINE | ID: mdl-32321277

ABSTRACT

BACKGROUND: Surveillance of sporadic renal angiomyolipomas is a growing issue for physicians and radiologists. Current treatment recommendations favor active surveillance. However, the evidence underlying these is based on small case series, which also typically include angiomyolipomas associated with tuberous sclerosis. PURPOSE: To evaluate the natural growth pattern of sporadic renal angiomyolipomas in patients without tuberous sclerosis. MATERIAL AND METHODS: A retrospective review was performed in three separate tertiary referral centers. A keyword search of each institutions PACS history was performed. Inclusion criteria were angiomyolipomas > 1 cm in size, three years of follow-up, and lesions requiring treatment before reaching three years of follow-up. Exclusion criteria included a diagnosis of tuberous sclerosis, pregnancy, prior treatment with embolization without any prior imaging, and lesions which were treated on presentation. Growth of the angiomyolipomas was evaluated on the basis of maximum dimension on initial and follow-up images. RESULTS: Sixty-three patients were identified in total, with 64 lesions eligible for inclusion. The majority of patients were women (55/63). The mean age at which the angiomyolipomas discovered was 56.4 years. Mean total growth was 0.085 mm and mean follow-up was 65.5 months. At initial measurement, the mean maximum dimension of the lesions in our cohort was 2.08 cm. After follow-up, this was 2.16 cm. The average rate of growth was 0.015 cm per year. CONCLUSION: Sporadic angiomyolipomas exhibit minimal, if any, natural growth. Current surveillance strategies could be relaxed.


Subject(s)
Angiomyolipoma/diagnostic imaging , Angiomyolipoma/pathology , Kidney Neoplasms/diagnostic imaging , Kidney Neoplasms/pathology , Tomography, X-Ray Computed/methods , Ultrasonography/methods , Adult , Aged , Disease Progression , Female , Follow-Up Studies , Humans , Kidney/diagnostic imaging , Kidney/pathology , Male , Middle Aged , Retrospective Studies
18.
Nat Commun ; 11(1): 5107, 2020 10 09.
Article in English | MEDLINE | ID: mdl-33037199

ABSTRACT

Engineered light-dependent switches provide uniquely powerful opportunities to investigate and control cell regulatory mechanisms. Existing tools offer high spatiotemporal resolution, reversibility and repeatability. Cellular optogenetics applications remain limited with diffusible targets as the response of the actuator is difficult to independently validate. Blue light levels commonly needed for actuation can be cytotoxic, precluding long-term experiments. We describe a simple approach overcoming these obstacles. Resonance energy transfer can be used to constitutively or dynamically modulate actuation sensitivity. This simultaneously offers on-line monitoring of light-dependent switching and precise quantification of activation-relaxation properties in intact living cells. Applying this approach to different LOV2-based switches reveals that flanking sequences can lead to relaxation times up to 11-fold faster than anticipated. In situ-measured parameter values guide the design of target-inhibiting actuation trains with minimal blue-light exposure, and context-based optimisation can increase sensitivity and experimental throughput a further 10-fold without loss of temporal precision.


Subject(s)
Molecular Imaging/methods , Optogenetics/methods , Phototropins/metabolism , Animals , Energy Transfer , Female , Fluorescence Resonance Energy Transfer/methods , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , HEK293 Cells , Hippocampus/cytology , Humans , Light , MAP Kinase Signaling System , Male , Neurons , Phototropins/analysis , Phototropins/genetics , Rats , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/metabolism
19.
Ir J Med Sci ; 189(3): 1097-1104, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32006389

ABSTRACT

BACKGROUND: Double-J stents are used to treat ureteric outflow obstruction. Deployed in antegrade or retrograde fashion, they relieve ureteric obstruction in several conditions including ureteric calculi, strictures and malignancy. Traditionally exchanged in an operating theatre (OT) under general anaesthetic (GA), more recently described is the technique of using fluoroscopic guidance under sedation. AIMS: To assess the efficacy and safety of retrograde double-J stent exchange in an interventional radiology (IR) setting in a tertiary oncology referral centre over a 7-year period. METHODS: Clinical data on 460 double-J stent exchanges in 126 female patients was acquired from the hospital electronic patient record. Four fellowship-trained interventional radiologists performed the procedures. A standard approach was used in conjunction with conscious sedation using midazolam and fentanyl. Use of the technique with certain anatomical variations is also described. RESULTS: Technical success rate was 96%. The main reasons for failure included failure to snare the stent (1.8%) and patient discomfort (1.1%). The overall complication rate was 5%: 5 category 1 (minor) and 18 category 3 outcomes, with the latter group requiring further intervention. Average screening time was 9.65 min and the average radiation dose was 2018.24 mGy/m2. We also demonstrate the successful use of this method in patients with unusual anatomy and ileal conduits. CONCLUSION: Fluoroscopic-guided retrograde double-J stent exchange is a safe and effective procedure that can be performed with a high degree of success using equipment and techniques used in daily IR practice. This approach precludes the need for GA, reduces OT utilisation and is well tolerated in a patient group for whom this procedure is typically palliative.


Subject(s)
Radiology, Interventional/methods , Stents/standards , Ureteral Obstruction/radiotherapy , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Ureter , Young Adult
20.
Acta Neuropsychiatr ; 31(6): 305-315, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31364522

ABSTRACT

OBJECTIVE: Despite its numerous side effects, clozapine is still the most effective antipsychotics making it an ideal reference substance to validate the efficacy of novel compounds for the treatment of schizophrenia. However, blood-brain barrier permeability for most new molecular entities is unknown, requiring central delivery. Thus, we performed a dose-finding study for chronic intracerebroventricular (icv) delivery of clozapine in mice. METHODS: Specifically, we implanted wild-type C57BL/6J mice with osmotic minipumps (Alzet) delivering clozapine at a rate of 0.15 µl/h at different concentrations (0, 3.5, 7 and 14 mg/ml, i.e. 0, 12.5, 25 and 50 µg/day). Mice were tested weekly in a modified SHIRPA paradigm, for locomotor activity in the open field and for prepulse inhibition (PPI) of the acoustic startle response (ASR) for a period of 3 weeks. RESULTS: None of the clozapine concentrations caused neurological deficits or evident gross behavioural alterations in the SHIRPA paradigm. In male mice, clozapine had no significant effect on locomotor activity or PPI of the ASR. In female mice, the 7 and 14 mg/ml dose of clozapine significantly affected both open field activity and PPI, while 3.5 mg/ml of clozapine increased PPI but had no effects on locomotor activity. CONCLUSION: Our findings indicate that 7 mg/ml may be the optimal dose for chronic icv delivery of clozapine in mice, allowing comparison to screen for novel antipsychotic compounds.


Subject(s)
Clozapine/administration & dosage , Clozapine/pharmacology , Dose-Response Relationship, Drug , Animals , Female , Infusions, Intraventricular , Male , Mice , Motor Activity/drug effects , Prepulse Inhibition/drug effects , Sex Characteristics
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