Mfsd7b facilitates choline transport and missense mutations affect choline transport function.

MFSD7b belongs to the Major Facilitator Superfamily of transporters that transport small molecules. Two isoforms of MFSD7b have been identified and they are reported to be heme exporters that play a crucial role in maintaining the cytosolic and mitochondrial heme levels, respectively. Mutations of MFSD7b (also known as FLVCR1) have been linked to retinitis pigmentosa, posterior column ataxia, and hereditary sensory and autonomic neuropathy. Although MFSD7b functions have been linked to heme detoxification by exporting excess heme from erythroid cells, it is ubiquitously expressed with a high level in the kidney, gastrointestinal tract, lungs, liver, and brain. Here, we showed that MFSD7b functions as a facilitative choline transporter. Expression of MFSD7b slightly but significantly increased choline import, while its knockdown reduced choline influx in mammalian cells. The influx of choline transported by MFSD7b is dependent on the expression of choline metabolizing enzymes such as choline kinase (CHKA) and intracellular choline levels, but it is independent of gradient of cations. Additionally, we showed that choline transport function of Mfsd7b is conserved from fly to man. Employing our transport assays, we showed that missense mutations of MFSD7b caused reduced choline transport functions. Our results show that MFSD7b functions as a facilitative choline transporter in mammalian cells.

Pudendal Nerve Block for Posthemorrhoidectomy Pain: A Prospective, Single-Blinded Randomized Control Trial.

BACKGROUND: Postoperative pain is common in hemorrhoidectomy patients. Local anesthetic given either as an intraoperative pudendal nerve block or as a local wound infiltration may help alleviate postoperative pain. OBJECTIVES: This study sought to determine whether the addition of an intraoperative pudendal nerve block to a perianal local wound infiltration and standardized analgesia regimen was superior to a perianal local wound infiltration and standardized analgesia regimen alone in reducing early postoperative pain following hemorrhoidectomy. The secondary objective was to measure differences between treatment groups in perceived perianal numbness, oral opioid requirements, and adverse events. DESIGN: This study was a prospective, single-blinded randomized controlled trial approved by the Eastern Health Human Research and Ethics Committee in Melbourne, Australia (registration number: E09/2014). SETTINGS: Patients were recruited across 3 Australian hospitals. PATIENTS: Eighty patients with symptomatic hemorrhoids requiring hemorrhoidectomy in colorectal surgical outpatient clinics were successfully recruited and enrolled in the study, with 1 patient later dropping out. INTERVENTION: Patients were randomly assigned to either the pudendal nerve block group or a control group. The pudendal nerve block group received 5 mL bupivacaine 0.5% with adrenaline 1:200,000 to both pudendal nerve trunks bilaterally. Both groups received 10 mL of the same local anesthetic injected into the post-hemorrhoidectomy wound bed. MAIN OUTCOME MEASURES: Visual analogue scales were used to record patient pain scores. Dichotomous (yes/no) answers were recorded for secondary objectives. RESULTS: There were no significant differences in postoperative pain between groups at 4 hours, 8 hours, 12 hours, or 24 hours. Additionally, there were no significant differences between groups with respect to perceived perianal numbness, oral opioid usage or adverse events. LIMITATIONS: The authors recognize that without a nerve stimulator, an argument can be made that the pudendal nerve block was not actually achieved. CONCLUSION: Pudendal nerve block does not appear to demonstrate additional benefit in post-hemorrhoidectomy pain reduction beyond local anesthetic to the wound. See Video Abstract at http://links.lww.com/DCR/B780. BLOQUEO DEL NERVIO PUDENDO PARA EL DOLOR POSHEMORROIDECTOMA ESTUDIO PROSPECTIVO, ALEATORIO, CONTROLADO, CIEGO: ANTECEDENTES:El dolor posoperatorio es común en pacientes luego de una hemorroidectomía. La administración de anestésico local como bloqueo del nervio pudendo intraoperatorio o infiltración local de la herida puede ayudar a aliviar el dolor posoperatorio.OBJETIVOS:Determinar si agregar un bloqueo intraoperatorio del nervio pudendo a una infiltración local perianal de la herida y un régimen de analgesia estandarizado fue superior a una infiltración local perianal de la herida más un régimen de analgesia estandarizado para reducir el dolor posoperatorio precoz después de una hemorroidectomía. Los objetivos secundarios incluyeron sensación de adormecimiento perianal, requerimientos de opioides orales y eventos adversos informados.DISEÑO:Este estudio fue un ensayo controlado aleatorio, prospectivo, ciego, aprobado por el Comité de Ética e Investigación en Humanos de Eastern Health en Melbourne, Australia (número de registro: E09 / 2014).ESCENARIO:Los pacientes fueron reclutados en tres hospitales australianos.PACIENTES:Ochenta pacientes se inscribieron con éxito en el estudio, y más tarde un paciente abandonó.INTERVENCIÓN:Los pacientes fueron asignados al azar al grupo de bloqueo del nervio pudendo o al grupo control. El grupo de bloqueo del nervio pudendo recibió 5 ml de bupivacaína al 0,5% con adrenalina 1: 200.000 en ambos troncos del nervio pudendo bilateralmente. Ambos grupos recibieron 10 ml del mismo anestésico local inyectado en el lecho de la herida posterior a la hemorroidectomía.PRINCIPALES VARIABLES ANALIZADAS:Se utilizaron escalas analógicas visuales para registrar las puntuaciones de dolor del paciente. Se registraron respuestas dicotómicas (sí / no) para los objetivos secundarios.RESULTADOS:No hubo diferencias significativas en el dolor posoperatorio entre los grupos a las 4, 8, 12 o 24 horas. Además, no hubo diferencias significativas entre los grupos con respecto al adromecimiento perianal percibido, el uso de opioides orales o los eventos adversos.LIMITACIONES:Sin el uso de un estimulador nervioso, se puede argumentar que el bloqueo del nervio pudendo no se logró realmente.CONCLUSIÓNES:El bloqueo del nervio pudendo no parece demostrar un beneficio adicional en la reducción del dolor posterior a la hemorroidectomía más allá del anestésico local en la herida. Consulte Video Resumen en http://links.lww.com/DCR/B780.

Bacterial survival and adhesion for formulating new oral probiotic foods.

Probiotics are defined as live microorganisms, which, when administered in adequate amounts, confer health benefits to the host. Traditionally, probiotic food research has heavily focused on the genera Bifidobacteria and Lactobacilli, along with their benefits for gut health. Recently with the identification of new probiotic strains specifically intended for oral health applications, the development of probiotic foods for oral health benefits has garnered interest, with a renewed focus on identifying new food formats for delivering probiotics. The development of novel oral probiotic foods is highly complex, as the composition of a food matrix dictates: (1) bacterial viability during production and shelf life and (2) how bacteria partition with components within a food matrix and subsequently adhere to oral cavity surfaces. At present, virtually no information is available on oral probiotic strains such as Streptococcus salivarius; specifically, how orally-derived strains survive under different food parameters. Furthermore, limited information exists on the partition behavior of probiotics with food components, governed by physico-chemical interactions and adhesion phenomena. This review aspires to examine this framework by providing a foundation with existing literature related to the common probiotic genera, in order to inform and drive future attempts of designing new oral probiotic food formats.

Utility of Spatial Point-Pattern Analysis Using Residential and Workplace Geospatial Information to Localize Potential Outbreak Sources.

Identifying the source of an outbreak facilitates its control. Spatial methods are not optimally used in outbreak investigation, due to a mix of the complexities involved (e.g., methods requiring additional parameter selection), imperfect performance, and lack of confidence in existing options. We simulated 30 mock outbreaks and compared 5 simple methods that do not require parameter selection but could select between mock cases' residential and workplace addresses to localize the source. Each category of site had a unique spatial distribution; residential and workplace address were visually and statistically clustered around the residential neighborhood and city center sites respectively, suggesting that the value of workplace addresses is tied to the location where an outbreak might originate. A modification to centrographic statistics that we propose-the center of minimum geometric distance with address selection-was able to localize the mock outbreak source to within a 500 m radius in almost all instances when using workplace in combination with residential addresses. In the sensitivity analysis, when given sufficient workplace data, the method performed well in various scenarios with only 10 cases. It was also successful when applied to past outbreaks, except for a multisite outbreak from a common food supplier.

Implementation of the Risk-Need-Responsivity Framework across the Juvenile Justice Agencies in Singapore.

The Risk-Need-Responsivity (RNR) framework is regarded as the forefront of offender rehabilitation in guiding youth offender risk assessment and interventions. This article discusses the juvenile justice system in Singapore and the local research that has been conducted in relation to the RNR framework and the associated Youth Level of Service (YLS) measures. It describes a journey that saw the implementation of the RNR framework across the juvenile justice agencies and highlights the challenges that were faced during the implementation process on the ground. Finally, the article concludes by providing future directions for the implementation of the RNR framework in Singapore.

Pilonidal sinus: an overview of historical and current management modalities.

Pilonidal disease is a common condition that commonly affects the younger adult population and is often seen in both the general practice and the hospital setting. Multiple treatment methods have gained and lost popularity over the last several decades, but more recent intervention principles show promising results. This article details the different methods of managing acute and chronic pilonidal disease ranging from treatments in the primary care setting to those in hospital theatres, with special attention to newer modalities of minimally invasive interventions. As a chronic illness that often affects those of working age, pilonidal disease can confer significant morbidity especially, but not limited to, a substantial amount of time off work. Treatment of chronic disease in particular, has evolved from midline techniques to off-midline techniques, with more recent developments offering promising solutions to reduce acute flare ups and hasten recovery time.

Robotic total colectomy and ileorectal anastomosis.

The benefits of minimally invasive approaches in colorectal surgery have been well demonstrated. However, some hesitancy remains with regards to the utilization of the robotic platform for total colectomies, mostly due to the perceived need for multiple re-dockings in multiquadrant surgery. This video aims to demonstrate how the robotic platform can be efficiently utilized in multiquadrant surgery without the need for multiple re-dockings, as well as some tips on how to overcome the potential challenges that may be encountered during this procedure.

Exposing the hidden complexity of stoichiometric and catalytic metathesis reactions by elucidation of Mg-Zn hybrids.

Studying seemingly simple metathesis reactions between ZnCl(2) and (t)BuMgCl has, surprisingly, revealed a much more complex chemistry involving mixed magnesium-zinc compounds that could be regarded as Mg-Zn hybrids. Thus, the reaction of equimolar amounts of ZnCl(2) and (t)BuMgCl reveals the formation of the unprecedented mixed Mg-Zn complex [(THF)(4)Mg(mu-Cl)(2)Zn((t)Bu)(Cl)] (1), as a result of the co-complexation of the two anticipated exchange products of the metathesis. This magnesium zincate adopts a contacted ion-pair structure, closely related to Knochel's pioneering "Turbo" Grignard reagents. Furthermore, a second coproduct identified in this reaction is the solvent-separated mixed magnesium-zinc chloride complex [{Mg(THF)(6)}(2+){Zn(2)Cl(6)}(2-)] (3) that critically diminishes the amount of ZnCl(2) available for the intended metathesis reaction to take place. In another surprising result, when the reaction is carried out by using an excess of 3 M equivalents of the Grignard reagent (closer to the catalytic conditions employed by synthetic chemists), solvent-separated magnesium trialkyl zincate [{Mg(2)Cl(3)(THF)(6)}(+){Zn((t)Bu)(3)}(-)] (4) is obtained that can be viewed as a model for the active species involved in the increasingly important organic transformations of Grignard reagents catalysed by ZnCl(2). Furthermore, preliminary reactivity studies reveal that complex 4 can be used as an effective new reagent for direct Zn-I exchange reactions that allow the preparation and structural identification of the magnesium tris(aryl) zincate [{Mg(2)Cl(3)(THF)(6)}(+){Zn(p-Tol)(3)}(-)] (5) that represents the first example of complete 3-fold activation of a zincate in a Zn-I exchange reaction which, in turn, can efficiently be used as a precursor for Negishi cross-coupling reactions.

Current perspectives on the management of lateral pelvic lymph nodes in rectal cancer.

Significant controversies exist with regards to the optimal management of lateral pelvic lymph nodes metastases (mLLN) in patients with low rectal cancer. The differing views held by Japanese and Western clinicians on the management of mLLN have been well documented. However, the adequacy of pelvic lymph node dissection (PLND) or neoadjuvant chemoradiation (NACRT) alone in addition to total mesorectal excision (TME) have recently come into question, due to the relatively high incidence of lateral local recurrences following PLND and TME, or NACRT and TME alone. Recently, a more selective approach to PLND has been suggested, involving a combination of neoadjuvant therapy, followed by PLND only to patients in whom the oncological benefit is likely to outweigh the risk of potential adverse events. A number of studies have attempted to retrospectively identify certain nodal characteristics on preoperative imaging, such as nodal size, appearance, and size reduction following neoadjuvant therapy. However, no consensus has been reached regarding the optimal criteria for a selective approach to PLND, partly due to the heterogeneity and retrospective nature of most of these studies. This review aims to provide an overview of recent evidence with regards to the diagnostic challenges, considerations for, and outcomes of the current management strategies for mLLN in rectal cancer patients.

Central Nervous System-related Conditions and Associated Healthcare Resource Use Among Japanese nmCRPC Patients Based on Retrospective Claims Data.

Background: Japanese patients with prostate cancer are typically treated with primary androgen deprivation therapy (ADT), most commonly administered as a combination of a luteinizing hormone-releasing hormone (LHRH) agonist and an antiandrogen (AA). Since LHRH agonists and AA therapy can be maintained for several years, the long-term effects of these treatments on patients must be carefully considered, including the risk of concomitant central nervous system (CNS) conditions which could affect treatment choices. Objective: To describe CNS-related concomitant conditions during ADT and/or AA treatment and the subsequent healthcare resource utilization in Japanese nonmetastatic castration-resistant prostate cancer (nmCRPC) patients. Methods: Patients diagnosed with nmCRPC and CNS-related conditions while on ADT and/or AA therapy between April 2009 and August 2017 were retrospectively followed up for a maximum of 2 years using a claims database. Results: A total of 455 patients (average age, 78.5 years), were included. The 3 most common concomitant CNS-related conditions were pain (~60% of events), insomnia (~30%), and headache (2%-3%). The frequency of CNS-related conditions in these patients increased approximately threefold after starting AA therapy (before, 969 events; after, 2802). On average, a patient had 10 episodes of concomitant CNS-related conditions in a year. Medical costs did not significantly increase due to CNS-related conditions. Discussion: The most frequently reported CNS-related conditions were pain, insomnia, and headaches. Furthermore, more concomitant CNS-related conditions 1 year after CRPC diagnosis and 1 year after starting AA treatment were recorded. Conclusion: Patients with nmCRPC experience an increase in the frequency of concomitant CNS-related conditions, including pain, insomnia, and headaches, after CRPC diagnosis or starting AA treatment. Future research should explore the causes of this increased frequency.

Treatment Sequence After Initiating Biologic Therapy for Patients With Rheumatoid Arthritis in Korea: A Nationwide Retrospective Cohort Study.

Objective: To evaluate treatment patterns and healthcare resource utilization (HCRU) after initiating biologic disease-modifying antirheumatic drugs (bDMARDs) in Korean patients with rheumatoid arthritis (RA). Methods: Patients newly diagnosed with RA in 2014 were identified and followed up on using the Korean National Health Insurance Database until 2018. The initial line of therapy (LOT) or LOT1 included patients treated with conventional DMARDs (cDMARD). Patients who started a bDMARD were assigned to LOT2 bDMARD. Those who moved from a bDMARD to a Janus kinase inhibitor were assigned to LOT3. Analyzed outcomes were treatment patterns and HCRU in LOT2 bDMARD. Results: The most prescribed initial bDMARD was a tumor necrosis factor inhibitor. Seventy-five percent of patients had changes in treatment after starting a bDMARD, such as addition/removal or switch of a DMARD, and transition to LOT3. For the first and second changes in LOT2 bDMARD, adding a cDMARD to a bDMARD was more common than switching to another bDMARD (7.98% vs. 2.93% for the first change, and 17.10% vs. 6.51% for the second change). Tocilizumab was the most common bDMARD that was switched to. Forty-eight percent of patients had at least one hospitalization after initiating bDMARDs. Of these patients, 64.3% were admitted due to RA-related reasons. Conclusion: This real-world study provides information on treatment characteristics of RA patients in Korea after starting a bDMARD. In contrary to guidelines, cDMARD addition was more often than bDMARD switches in daily clinical practice.

Vaccine wastage in Ghana, Mozambique, and Pakistan: An assessment of wastage rates for four vaccines and the context, causes, drivers, and knowledge, attitudes and practices for vaccine wastage.

Vaccine procurement costs comprise a significant share of immunization program costs in low- and middle-income countries, yet not all procured vaccines are administered. Vaccine wastage occurs due to vial breakage, excessive heat or freezing, expiration, or when not all doses in a multidose vial are used. Better estimates of vaccine wastage rates and their causes could support improved management of vaccine stocks and reduce procurement costs. This study examined aspects of wastage for four vaccines at service delivery points in Ghana (n = 48), Mozambique (n = 36), and Pakistan (n = 46). We used prospective data from daily and monthly vaccine usage data entry forms, along with cross-sectional surveys, and in-depth interviews. The analysis found that estimated monthly proportional open-vial wastage rates for vaccines in single-dose vials (SDV) or in multi-dose vials (MDV) that can be kept refrigerated up to four weeks after opening ranged from 0.08 % to 3 %. For MDV where remaining doses are discarded within six hours after opening, the mean wastage rates ranged from 5 % to 33 %, with rates being highest for measles containing vaccine. Despite national-level guidance to open a vaccine vial even when only one child is present, vaccines in MDV that are discarded within six hours of opening are sometimes offered less frequently than vaccines in SDV or in MDV where remaining doses can be used for up to 4 weeks. This practice can lead to missed opportunities for vaccination. While closed-vial wastage at service delivery points (SDPs) was relatively rare, individual instances can result in large losses, suggesting that monitoring closed-vial wastage should not be neglected. Health workers reported insufficient knowledge of vaccine wastage tracking and reporting methods. Improving reporting forms would facilitate more accurate reporting of all causes of wastage, as would additional training and supportive supervision. Globally, decreasing doses per vial could reduce open-vial wastage.

Factors associated with self-reported burnout level in allied healthcare professionals in a tertiary hospital in Singapore.

BACKGROUND: Burnout has adverse implications in healthcare settings, compromising patient care. Allied health professionals (AHPs) are defined as individuals who work collaboratively to deliver routine and essential healthcare services, excluding physicians and nurses. There is a lack of studies on burnout among AHPs in Singapore. This study explored factors associated with a self-reported burnout level and barriers to seeking psychological help among AHPs in Singapore. METHODS: We conducted a cross-sectional study in a sample of AHPs in a tertiary hospital from October to December 2019. We emailed a four-component survey to 1127 eligible participants. The survey comprised four components: (1) sociodemographic characteristics, (2) Maslach Burnout Inventory (MBI-HSS), (3) Areas of Worklife Survey, and (4) Perceived Barriers to Psychological Treatment (PBPT). We performed a multiple logistic regression analysis to identify factors associated with burnout. Adjusted odds ratios (AORs) and associated 95% confidence intervals (CIs) were computed. RESULTS: In total, 328 participants completed the questionnaire. The self-reported burnout level (emotional exhaustion>27 and/or depersonalization>10) was 67.4%. The majority of the respondents were female (83.9%), Singaporean (73.5%), aged 40 years and below (84.2%), and Chinese ethnicity (79.9%). In the multiple logistic regression model, high burnout level was negatively associated with being in the age groups of 31 to 40 (AOR 0.39, 95% CI 0.16-0.93) and 40 years and older (AOR 0.30, 95% CI 0.10-0.87) and a low self-reported workload (AOR 0.35, 95% CI 0.23-0.52). High burnout level was positively associated with a work experience of three to five years (AOR 5.27, 95% CI 1.44-20.93) and more than five years (AOR 4.24; 95% CI 1.16-16.79. One hundred and ninety participants completed the PBPT component. The most frequently cited barriers to seeking psychological help by participants with burnout (n = 130) were 'negative evaluation of therapy' and 'time constraints.' CONCLUSIONS: This study shows a high self-reported burnout level and identifies its associated factors among AHPs in a tertiary hospital. The findings revealed the urgency of addressing burnout in AHPs and the need for effective interventions to reduce burnout. Concurrently, proper consideration of the barriers to seeking help is warranted to improve AHPs' mental well-being.

Breast cancer subtypes in Australian Chinese women.

BACKGROUND: It has been suggested that Chinese patients with breast cancer present at a younger age compared to the general Australian population, with tumour pathological characteristics that carry less favourable outcomes. This study was aimed to investigate if a substantial difference in breast cancer subtypes exists between the Australian Chinese population and the general Australian population. METHODS: All patients with breast cancer treated by two of the authors (consultant breast surgeons) at Eastern Health, Victoria between 2010 and 2016 were identified through the BreastSurgANZ Quality Audit database. Australian Chinese patients were further identified through outpatient records and registration information. Medical histories were examined to obtain patient demographics, tumour characteristics and outcome. Patient and tumour characteristics between the Australian Chinese population were then compared to the general Australian population. RESULTS: A total of 97 Australian Chinese patients with breast cancer were identified out of 582 patients. Mean age at diagnosis was 56.7 years, approximately 6 years younger than the general Australian population. There was a statistically significant difference in incidence of Luminal A tumours with 25 patients (25.77%) from the Chinese group affected compared to 310 patients (63.92%) from the general group (P < 0.001). There was no significant difference in proportions of the other tumour subtypes between the two groups. CONCLUSION: Australian Chinese breast cancer patients present at a younger age compared to the general Australian population, with a smaller proportion of patients having Luminal A tumours.

Comparison of flow pressures in different 3-way infusion devices: an in-vitro study.

BACKGROUND: The use of multiple infusions through one cannula is an increasingly common practice in anaesthesia. High pressures in the line often lead to occlusion alarms and pump disconnection. In this study, we aim to determine the pressures generated in common 3-way infusion devices, using simple low-cost equipment available and currently in use in the operating theatre environment. METHODS: We compared three different common and commercially available 3-way infusion devices that allowed multiple infusions through one cannula in vitro. One with anti-siphon valves, one without valves, and serial extension sets with side ports connected in series. An invasive blood pressure transducer was used to monitor line pressure. Seven different infusion rates were used to simulate different infusions. RESULTS: 3-way infusion devices with anti-siphon valves have 5.5 times the infusion pressures compared to devices without valves (P < 0.001). The highest pressures obtained across all devices were at the highest flow rate studied (400 ml/hr); this was 243 mmHg in the 3-way device with anti-siphon valves, compared to only 44 mmHg in the 3-way device without valves and 36 mmHg in the serial extension sets. Serial extension sets have the lowest pressures across all flow rates when compared to 3-way devices without valves. (P = 0.0001). CONCLUSIONS: The presence of anti-siphon valves generate very high pressures in infusion lines that can contribute to occlusion alarm disconnection of a pump. However, when measured alone and in-vitro, these pressures are not sufficient to trigger occlusion alarms. There are 3-way infusion devices without anti-siphon valves that have lower line pressures, but clinicians should be aware of negative pressure scenarios which can lead to siphoning when using them.