Use of a dosimetry-based RAI protocol for treatment of benign hyperthyroidism optimises response while minimising exposure to ionising radiation.

BACKGROUND: The optimal treatment strategy for radioiodine (RAI) treatment protocols for benign hyperthyroidism remains elusive. Although individualised activities are recommended in European Law, many centres continue to provide fixed activities. Our institution implemented a dosimetry protocol in 2016 following years of fixed dosing which facilitates the calculation of individualised activities based on thyroid volume and radioiodine uptake. METHODS: This was a retrospective study comparing success rates using a dosimetry protocol targeting an absorbed dose of 150 Gy for Graves' disease (GD) and 125 Gy for Toxic Multinodular Goiter (TMNG) with fixed dosing (200MBq for GD and 400MBq for TMNG) among 204 patients with hyperthyroidism. Success was defined as a non-hyperthyroid state at 1 year for both disease states. Results were analysed for disease specific or patient specific modulators of response. RESULTS: This study included 204 patients; 74% (n = 151) received fixed activities and 26% (n = 53) of activities administered were calculated using dosimetry. A dosimetry-based protocol was successful in 80.5% of patients with GD and 100% of patients with TMNG. Differences in success rates and median activity administered between the fixed (204Mbq) and dosimetry (246MBq) cohort were not statistically significant (p = .64) however 44% of patients with GD and 70% of patients with TMNG received lower activities following treatment with dosimetry as opposed to fixed activities. Use of dosimetry resulted in successful treatment and reduced RAI exposure for 36% of patients with GD, 70% of patients with TMNG, and 44% of patients overall. CONCLUSION: This retrospective clinical study demonstrated that treatment with a dosimetry-based protocol for TMNG and GD achieved comparable success rates to fixed protocols while reducing RAI exposure for over a third of patients with GD and most patients with TMNG. This study also highlighted that RAI can successfully treat hyperthyroidism for some patients with activities lower than commonplace in clinical practise. No patient or disease specific modulators of treatment response were established in this study; however, the data supports a future prospective trial which further scrutinises the individual patient factors governing treatment response to RAI.

S-BIRD: A Novel Critical Multi-Class Imagery Dataset for Sewer Monitoring and Maintenance Systems.

Computer vision in consideration of automated and robotic systems has come up as a steady and robust platform in sewer maintenance and cleaning tasks. The AI revolution has enhanced the ability of computer vision and is being used to detect problems with underground sewer pipes, such as blockages and damages. A large amount of appropriate, validated, and labeled imagery data is always a key requirement for learning AI-based detection models to generate the desired outcomes. In this paper, a new imagery dataset S-BIRD (Sewer-Blockages Imagery Recognition Dataset) is presented to draw attention to the predominant sewers' blockages issue caused by grease, plastic and tree roots. The need for the S-BIRD dataset and various parameters such as its strength, performance, consistency and feasibility have been considered and analyzed for real-time detection tasks. The YOLOX object detection model has been trained to prove the consistency and viability of the S-BIRD dataset. It also specified how the presented dataset will be used in an embedded vision-based robotic system to detect and remove sewer blockages in real-time. The outcomes of an individual survey conducted at a typical mid-size city in a developing country, Pune, India, give ground for the necessity of the presented work.

Use of Thyroid Hormones in Hypothyroid and Euthyroid Patients: A THESIS questionnaire survey of members of the Irish Endocrine Society.

BACKGROUND: Replacement of thyroid hormones (TH) with Levothyroxine (LT4) is the treatment of choice for hypothyroidism, however, there are aspects of treatment where uncertainties exist and practice varies. Factors influencing initiation and choice of TH replacement may impact patient satisfaction, safety, and health care costs. METHODS: The aim of the study was to examine the attitudes of Irish endocrinologists regarding the treatment of hypothyroid and euthyroid patients with TH. Members of the Irish Endocrine Society (IES) were invited to participate in an online survey. RESULTS: Forty-eight invitations were sent, and 39 (81.3%) participants responded. All respondents favoured LT4 tablet therapy for treatment of hypothyroidism, but 20.5% prescribed combination therapy (LT4 and liothyronine), and 13% regularly used desiccated thyroid extract. A significant proportion (51%) might prescribe TH in euthyroid patients; 41% for thyroid auto-antibody positive women seeking pregnancy, 18% for goitre and 5% for unexplained fatigue. Many (38%) consider combination therapy in patients with persistent symptoms. Respondents reported seeing LT4 treated patients with persistent symptomatology more frequently and perceive psychosocial factors and comorbidities to be the most common reasons for such symptoms. CONCLUSION: LT4 tablets are the treatment of choice for hypothyroidism in Ireland. Approximately a third of Irish endocrinologists either regularly use, or would consider, liothyronine for hypothyroid patients. A significant proportion would give TH to euthyroid individuals in specific circumstances. The prescription of TH amongst Irish endocrinologists was generally in keeping with recommended practice, and areas where practice deviated from guidance were typically where evidence was conflicting or insufficient.

Atlantic DIP: is weight gain less than that recommended by IOM safe in obese women with gestational diabetes mellitus?

BACKGROUND/OBJECTIVES: The Institute of Medicine (IOM) recommends gestational weight gain (GWG) of 5-9 kg in women with a body mass index (BMI) ≥ 30 kg/m2. Debate continues as to whether GWG less than that recommended is safe in women with gestational diabetes mellitus (GDM). The study objective was to examine maternal and infant outcomes for obese women with GDM who lost weight or gained 0-5 kg during pregnancy. SUBJECTS/METHODS: A 7-year retrospective cohort study of pregnancy outcomes for obese women with GDM recorded in the Atlantic Diabetes in Pregnancy database was conducted. We examined pregnancy outcomes for mothers with GDM and a BMI ≥ 30 who either lost weight or gained 0-5 kg (Group 1, n = 237) and women who gained 5-9 kg (Group 2, n = 77). We further divided groups 1 and 2 into women treated by diet only (GDM-D) (n = 120) and those requiring additional treatment with insulin (GDM-I) (n = 194). RESULTS: GDM-D women in Group 1 were more likely to deliver earlier (38.9 vs 39.8 weeks, p < 0.01), to develop pregnancy induced hypertension (PIH) (15.4% v 0%; p = 0.02) or have a post-partum haemorrhage (PPH) (13.2% vs 0, p = 0.03) compared to women in Group 2. Rates of prematurity were higher in group 1 vs 2 (14.3% vs 0%, p = 0.03). However, further logistic regression analysis adjusted for smoking status, family history of diabetes, ethnicity and age determined no significant difference in maternal or infant outcomes for women in Group 1 compared to those in Group 2. CONCLUSION: In our population, weight gain less than IOM guideline appears safe and is not associated with any further increase in adverse outcomes. However, validation through a prospective study with a larger obese GDM cohort is required before the findings presented here could be recommended for routine clinical use.

Unusual case of antiphospholipid syndrome presenting as adrenal insufficiency.

A 64-year-old man presented to the emergency department with generalised fatigue and dizzy spells. His background history includes a previous admission with right leg deep vein thrombosis, provoked by pneumonia. Laboratory results showed evidence of hyponatremia and hyperkalaemia. A synacthen test was performed that indicated hypoadrenalism. CT of his abdomen revealed enlarged adrenal glands bilaterally. Adrenal antibodies and positron emission tomography (PET) scan were performed to assess the cause of enlarged adrenals. PET scan showed no evidence of increased uptake. Adrenal antibodies were found to be negative. Tuberculous (TB) adrenalitis was the principle differential diagnosis. TB QuantiFERON was strongly positive. Following 9 months of TB treatment, surveillance CT scan indicated a significant reduction in adrenal gland size. However, subsequent events culminated in a retrospective review of CT scans questioning the initial clinical diagnosis and suggesting that the observed adrenal gland enlargement was secondary to bilateral adrenal infarction and haemorrhage. Equally, the subsequently observed marked reduction in adrenal gland size was not secondary to an assumed response to TB therapy, but rather the sequela of infracted atrophied adrenal glands, as a manifestation of the underlying antiphospholipid syndrome (APS). The case highlights the importance of recognising adrenal insufficiency in patients with a history of APS. It also illustrates the role of multidisciplinary meetings in the management of such complex cases.

Knowledge, Perceptions and Concerns of Diabetes -Associated Complications Among Individuals Living with Type 1 and Type 2 Diabetes Mellitus.

The purpose of this study was to investigate the knowledge, perceptions and concerns of individuals living with diabetes mellitus regarding the disorder and its associated long-term health complications. Individuals living with type 1 (N = 110) and type 2 (N = 100) diabetes were surveyed at the Diabetes Centre at University Hospital Galway (Ireland). A questionnaire was used to record respondent's perceptions and concerns about living with diabetes and developing associated long-term health complications, especially diabetes-induced osteopathy. Participants' responses revealed a variety of perspectives. Individuals with type 1 diabetes had a deeper understanding of the aetiology of diabetes and were more concerned about its complications than individuals with type 2 diabetes. The most recognized complications identified by the participants were retinopathy (92% type 1; 83% type 2), amputations (80% type 1; 70% type 2) and nephropathy (83% type 1; 63% type 2). Diabetes-related osteopathy was under-recognized, with 37% (type 1) and 23% (type 2) of respondents identifying bone fractures as a diabetes-related complication. Enhancing the patient awareness of this under-recognized diabetes-associated complication and ensuring that preventative measures are incorporated within health care programmes may offer methodologies to address this complication clinically.

Poly[2,2'-(4,4'-bipyridine)-5,5'-bibenzimidazole] functionalization of carbon black for improving the oxidation stability and oxygen reduction reaction of fuel cells.

The rapid oxidation of carbon black (CB) is a major drawback for its use as a catalyst support in polymer electrolyte fuel cells. Here, we synthesize poly[2,2'-(4,4'-bipyridine)-5,5'-bibenzimidazole] (BiPyPBI) as a conducting polymer and use it to functionalize the surface of CB and homogenously anchor platinum metal nanoparticles (Pt-NPs) on a CB surface. The as-prepared materials were confirmed by different spectroscopic techniques, including nuclear magnetic resonance spectroscopy, energy-dispersive X-ray, thermal gravimetric analysis, and scanning-transmittance microscopy. The as-fabricated polymer-based CB catalyst showed an electrochemical surface area (ECSA) of 63.1 cm2 mgPt -1, giving a catalyst utilization efficiency of 74.3%. Notably, the BiPyPBI-based CB catalyst exhibited remarkable catalytic activity towards oxygen reduction reactions. The onset potential and the diffusion-limiting current density reached 0.66 V and 5.35 mA cm-2, respectively. Furthermore, oxidation stability testing showed a loss of only 16% of Pt-ECSA for BiPyPBI-based CB compared to a 36% loss of Pt-ECSA for commercial Pt/CB after 5000 potential cycles. These improvements were related to the synergetic effect between the nitrogen-rich BiPyPBI polymer, which promoted the catalytic activity through the structural nitrogen atoms, and demolished the degradation of CB via the wrapping process.

Tumour Lysis Syndrome and Partial Remission Occurring After Administration of a Test Dose of Obinutuzumab.

Chronic lymphocytic leukaemia (CLL) is one of the most common haematological malignancies worldwide, with an increasing prevalence in the elderly population. Obinutuzumab is a type II anti-CD20 monoclonal antibody which showed superiority over rituximab in combination chemotherapy with chlorambucil for the treatment of CLL in the CLL11 trial (NCT01010061) and is becoming part of standard first line treatment for CLL in the elderly based on its potent efficacy and benign safety profile. We report the case of a chemotherapy naive patient who develop tumour lysis syndrome despite appropriate prophylaxis, and had partial remission of her disease after receiving only the initial test dose of obinutuzumab. LEARNING POINTS: Chemotherapy-induced tumour lysis syndrome is a serious complication that can occur after even a small dose of chemotherapy.Chronic lymphocytic leukaemia patients with strongly positive CD20 cells can be more sensitive to obinutuzumab chemotherapy.

Hypotensive effect of Gentiana floribunda is mediated through Ca++ antagonism pathway.

BACKGROUND: Gentiana floribunda was investigated for the possible hypotensive and vasodilator activities in an attempt to rationalize its traditional use in hypertension. METHODS: The crude extract of Gentiana floribunda (Gf.Cr) was studied in anaesthetized rats and isolated thoracic aorta tissues. RESULTS: Gf.Cr which tested positive for presence of flavonoids, saponins, sterols, tannins and terpenes caused dose-dependent (3.0-100 mg/kg) fall in arterial blood pressure (BP) of rats under anaesthesia. In rat aortic ring preparations denuded of endothelium, Gf.Cr at concentration range of 1.0-10 mg/mL relaxed high K+ (80 mM) and phenylephrine (PE, 1 µM)-induced contractions and shifted Ca++ dose-response curves to right, similar to that caused by verapamil. It also suppressed PE (1 µM) control peak responses at 0.3-1.0 mg/mL, obtained in Ca++-free medium, as exhibited by verapamil. Pre-treatment of tissues with Gf.Cr produced rightward non-parallel shift of PE-curves with decline of maximum contractile response. The vasodilator effect of Gf.Cr was endothelial-independent, as it was not blocked by Nω-nitro-L-arginine methyl ester hydrochloride, atropine and indomethacin in endothelium-intact aortic tissues. CONCLUSIONS: These data indicate that BP-lowering action of Gentiana floribunda occurred via Ca++ antagonism (inhibition of Ca++ ingress and release from intracellular stores), which provides pharmacological basis to justify its effectiveness in hypertension.

Vasodilator effect of Phlomis bracteosa constituents is mediated through dual endothelium-dependent and endothelium-independent pathways.

This study describes the vasorelaxant potential of some pure compounds isolated from Phlomis bracteosa L. marrubiin, phlomeoic acid, and two new constituents labeled as RA and RB. In rat thoracic aortic rings denuded of endothelium, marrubiin, phlomeoic acid, RA, and RB caused relaxation of high K(+) (80 mM) and phenylephrine (1 µM)-induced contractions at the concentration range of 1.0-1000 µg/mL. Marrubiin, phlomeoic acid, RA, and RB concentration dependently (3.0-10 µg/mL) shifted the Ca(++) curves to the right obtained in Ca(++)-free medium. The vasodilator effect of marrubiin, phlomeoic acid, RA, and RB was partially blocked by N(ω)-nitro-L-arginine methyl ester in endothelium-intact aorta preparations. These results reveal that P. bracteosa constituents: marrubiin, phlomeoic acid, RA, and RB exhibit vasodilator action occurred via a combination of endothelium-independent Ca(++) antagonism and endothelium-dependent N(ω)-nitro-L-arginine methyl ester-sensitive nitric oxide-modulating mechanism.

Malabaricone C from Myristica cinnamomea exhibits anti-quorum sensing activity.

A methanol-soluble extract of the bark of Myristica cinnamomea was found to exhibit anti-quorum sensing activity, and subsequent bioassay-guided isolation led to the identification of the active compound malabaricone C (1). Compound 1 inhibited violacein production by Chromobacterium violaceum CV026 when grown in the presence of a cognate signaling molecule, N-3-oxohexanoyl-homoserine lactone. Furthermore, 1 inhibited the quorum sensing-regulated pyocyanin production and biofilm formation in Pseudomonas aeruginosa PAO1. These results suggest that the anti-quorum sensing activity of 1 and related molecules should be investigated further.

Purification and biochemical characterization of alkaline serine protease from Caesalpinia bonducella.

A high molecular weight serine protease has been purified to electrophoretic homogeneity from the seeds of Caesalpinia bonducella Flem. (Caesalpiniaceae) by the combination of size exclusion and ion exchange chromatography. About 524 fold purification was achieved with an overall recovery of 6.8%. The specific activity was found to be 86 U/mg/min at pH 8.0. The calculated K(m) and V(max) were 1.66 mg/mL and 496.68 units/min per mg of protein, respectively. The molecular mass was estimated to be about 63 kDa by sodium dodecyl sulfate PAGE. The enzyme showed optimum activity at pH 8.0 and exhibited its highest activity at 40 degrees C. The enzyme was strongly inhibited by 2mM phenylmethylsulfonyl fluoride (PMSF), suggesting the presence of a serine residue at the active site. PMSF showed a pure competitive type of inhibition with the serine protease enzyme. It was observed that enzyme activity was enhanced in the presence of dications and was active against a variety of modified substrates and natural proteins.