Integrating morphology and physiology of the key endocrine organ during tadpole development: The interrenal gland.

Indirect development is widespread in anurans and is considered an ancestral condition. The metamorphosis of larvae into juveniles involves highly coordinated morphological, physiological, biochemical, and behavioral changes, promoted by the thyroid hormone and interrenal corticosteroids. Stress response to environmental changes is also mediated by corticosteroids, affecting the timing and rate of metamorphosis and leading to great developmental plasticity in tadpoles. Given the potential effect of interrenal gland ontogeny alterations on metamorphosis and the lack of studies addressing both the morphology and endocrinology of this gland in tadpoles, we present corticosterone (CORT) production and histological changes through the ontogeny of interrenal gland in the generalized pond-type tadpole of Rhinella arenarum (Anura, Bufonidae). This species shows the highest concentration of whole-body CORT by the early climax when drastic metamorphic changes begin. This is coincident with the morphological differentiation of steroidogenic cells and the formation of interrenal cords. By this stage, steroidogenic cells have a shrunken cytoplasm, with a significantly higher nucleus-to-cell diameter ratio. The lowest CORT concentration during premetamorphosis and late climax is associated with small undifferentiated cells with lipid inclusions surrounding large blood vessels between kidneys, and with cords of differentiated steroidogenic cells with a significantly lower nucleus-to-cell diameter ratio, respectively. Our study characterizes the morphological and physiological pattern of interrenal gland development, showing an association between certain histological and morphometric characteristics and CORT levels. Variations in this morpho-physiological pattern should be considered when studying the phenotypic plasticity or variable growth rates of tadpoles.

Covid-19 and the Impact on Referrals to Psychiatry in those 65 years and Older.

Aim To measure the impact of Covid-19 on the mental health of those 65 years and older, referrals to psychiatry in this Emergency Department (ED) were examined. This was likely the 'tip of the iceberg' in difficulties in this cohort and may predict patterns in a future 'tsunami' of cases. Methods A review of referrals from ED in those ≥ 65 years was conducted, from April to September in 2019 and 2020. Number of presentations, referral reason, alcohol issues, presentation method and assessment outcome were examined. Results From May 2020, there was increased referrals in all ages, except those aged 65 and older. Only 6.7% of referrals were ≥ 65years in 2020 (11% in 2019), with more referred for anxiety, suicidality and overdose, with no BPSD (behavioural and psychological symptoms of dementia) referrals recorded. There was an increase presenting with psychosis secondary to mental illness, alcohol issues and brought by emergency services, with a decrease in those linked with services. Conclusions There was a probable unmet burden of psychiatric needs in this age-group with potentially increased distress and reduced supports, in less presentations. Difficulties providing services during this period and lack of presentations such as BPSD, raises concerns for older patients and a future 'tsunami' of presentations.

Investigation of reference levels and radiation dose associated with abdominal EVAR (endovascular aneurysm repair) procedures across several European Centres.

OBJECTIVES: Endovascular aneurysm repair (EVAR) is considered the treatment of choice for abdominal aortic aneurysms with suitable anatomy. In order to improve radiation safety, European Directive (2013/59) requires member states to implement diagnostic reference levels (DRLs) in radio-diagnostic and interventional procedures. This study aimed to determine local DRLs for EVAR across five European centres and identify an interim European DRL, which currently remains unestablished. METHODS: Retrospective data was collected for 180 standard EVARs performed between January 2014 and July 2015 from five specialist centres in Ireland (n=2) and Italy (n=3). Data capture included: air kerma-area product (PKA), total air kerma at the reference point (Ka,r), fluoroscopic time (FT), number of acquisitions, frame rate of acquisition, type of acquisition, patient height, weight, and gender. RESULTS: The mean values for each site A, B, C, D, and E were: PKAs of 4343 ± 994 µGym2, 18,200 ± 2141 µGym2, 11,423 ± 1390 µGym2, 7796 ± 704 µGym2, 31,897 ± 5798 µGym2; FTs of 816 ± 92 s, 950 ± 150 s, 708 ± 70 s, 972 ± 61 s, 827 ± 118 s; and number of acquisitions of 6.72 ± 0.56, 10.38 ± 1.54, 4.74 ± 0.19, 5.64 ± 0.36, 7.28 ± 0.65, respectively. The overall pooled 75th percentile PKA was 15,849 µGym2. CONCLUSION: Local reference levels were identified. The pooled data has been used to establish an interim European DRL for EVAR procedures. KEY POINTS: • Abdominal endovascular aneurysm repair (EVAR) requires the use of ionising radiation. • EVAR is a minimally invasive procedure for the treatment of abdominal aortic aneurysms. • Diagnostic reference levels (DRLs) are used to monitor patient radiation exposure. • Radiation dose data was collected from five European centres for EVAR procedures. • Local DRLs have been determined and an interim European DRL is proposed.

Comparison of colour duplex ultrasound with computed tomography to measure the maximum abdominal aortic aneurysmal diameter.

Introduction. Maximum diameter of an abdominal aortic aneurysm (AAA) is the main indication for surgery. This study compared colour duplex ultrasound (CDU) and computed tomography (CT) in assessing AAA diameter. Patients and Methods. Patients were included if they had both scans performed within 90 days. Pearson's correlation coefficient, paired t-test, and limits of agreement (LOA) were calculated for the whole group. Subgroup analysis of small (<5.0 cm), medium (5.0-6.5 cm), and large (>6.5 cm) aneurysms was performed. A P value of <0.05 was considered statistically significant. Results. 389 patients were included, giving 130 pairs of tests for comparison. Excellent correlation was in the whole group (r = 0.95) and in the subgroups (r = 0.94; 0.69; 0.96, resp.). Small LOA between the two imaging modalities was found in all subgroups. Conclusion. Small aneurysms can be accurately measured using CDU. CDU is preferable for small AAAs, but cannot supplant CT for planning aortic intervention.

Use of colour duplex ultrasound as a first line surveillance tool following EVAR is associated with a reduction in cost without compromising accuracy.

INTRODUCTION: CT scanning remains the postoperative surveillance imaging modality of choice following EVAR. Concerns regarding cost, exposure to ionising radiation and intravenous contrast have led to a search for a less expensive, equally efficacious and safer method of monitoring EVAR patients after endograft deployment. This study evaluated the cost saving obtained if CDUS was employed as a first line surveillance tool following EVAR, as well as comparing the two entities in terms of efficacy. PATIENTS & METHODS: Postoperative surveillance CTs and CDUS scans in the 145 patients who have undergone EVAR from 1st June 2003 to 1st July 2010 were compared for the detection of endoleak and determination of residual sac size. RESULTS: Adopting a protocol where CDUS was employed as the first line surveillance tool following EVAR would result in a reduction in the number of postoperative CTs required in 2010 from 235 to 36. Based on 2010 costings, this would equate to an estimated reduction in expenditure from €117,500 to €34,915 a saving of €82,585. CDUS had a sensitivity of 100% and a specificity of 85% in the detection of endoleaks compared to CT. The positive predictive value was 28% and negative predictive value 100%. The Pearson Coefficient correlation of 0.96 indicates a large degree of correlation between CDUS and CT when measuring residual aneurysm size following EVAR. CONCLUSION: CDUS can replace CT as the first line surveillance tool following EVAR. This is associated with a significant reduction in the cost of surveillance without any loss of imaging accuracy.

Eversion endarterectomy for external iliac artery occlusive disease.

INTRODUCTION: The advent of effective endovascular techniques has revolutionized the treatment of iliac occlusive disease. Long-segment iliac occlusions remain technically difficult to treat, particularly in the presence of femoral disease. Iliac endarterectomy is an established procedure for the treatment of iliac occlusive disease, but it has been suggested that in the era of effective endovascular intervention, its role is limited. METHODS: A review of all patients who had eversion endarterectomy of the external iliac artery from a single institution between 2000 and 2008. RESULTS: Twenty-one patients (18 male) underwent eversion external iliac endarterectomy, 15 for external iliac and 6 for iliofemoral disease. Mean age was 64.7 years (range: 46-78 years) and the modal American Society of Anaesthesiologists (ASA) grade was 3. The indications were critical ischemia (n = 16) and disabling claudication (n = 5). Twelve had adjunctive procedures. The mean follow-up was 25.3 months (range: 1-59 months). There were no technical failures. Seventeen patients had significant improvement in symptoms and three had moderate improvement. The cumulative primary patency at 1 year was 81%. One patient had no improvement (because of infrainguinal occlusive disease), and subsequently required femoro-popliteal bypass. There was no systemic morbidity within 30 days. There was 1 in-hospital death from sudden cardiac arrest (47 days postoperatively). Six patients died during follow-up (from unrelated illness). CONCLUSION: Eversion external iliac endarterectomy is an effective means of treating iliofemoral occlusive disease with excellent short-term outcomes and a low complication rate in a cohort with high levels of comorbidity.

The incidence and course of depression in bereaved youth 21 months after the loss of a parent to suicide, accident, or sudden natural death.

OBJECTIVE: This study examined effects of bereavement 21 months after a parent's death, particularly death by suicide. METHOD: The participants were 176 offspring, ages 7-25, of parents who died by suicide, accident, or sudden natural death. They were assessed 9 and 21 months after the death, along with 168 nonbereaved subjects. RESULTS: Major depression and alcohol or substance abuse 21 months after the parent's death were more common among bereaved youth than among comparison subjects. Offspring with parental suicide or accidental death had higher rates of depression than comparison subjects; those with parental suicide had higher rates of alcohol or substance abuse. Youth with parental suicide had a higher incidence of depression than those bereaved by sudden natural death. Bereavement and a past history of depression increased depression risk in the 9 months following the death, which increased depression risk between 9 and 21 months. Losing a mother, blaming others, low self-esteem, negative coping, and complicated grief were associated with depression in the second year. CONCLUSIONS: Youth who lose a parent, especially through suicide, are vulnerable to depression and alcohol or substance abuse during the second year after the loss. Depression risk in the second year is mediated by the increased incidence of depression within the first 9 months. The most propitious time to prevent or attenuate depressive episodes in bereaved youth may be shortly after the parent's death. Interventions that target complicated grief and blaming of others may also improve outcomes in symptomatic youth with parental bereavement.

Transfusion requirements and outcomes in patients undergoing abdominal aortic surgery using intra-operative cell salvage.

BACKGROUND: Intraoperative cell salvage (ICS) is the recovery, anticoagulation, filtration and reinfusion of blood lost during surgery. The aim of this study is to determine the safety and efficacy of ICS in emergency and elective abdominal aortic surgery. METHODS: This study reviews volumes of blood loss, blood salvaged with ICS, allogenic blood requirements, and clinical outcomes in patients undergoing abdominal aortic surgery using ICS. RESULTS: Seventy-nine patients undergoing abdominal aortic surgery are included. Supplemental allogenic blood was not required in 45/79 (57%) of all patients. Transfusion with allogenic blood was not necessary in 41/63 (66%) of elective abdominal aortic aneurysm repairs. ICS was associated with no major complications. CONCLUSION: ICS is a safe procedure and substantially reduces the need for blood transfusion in patients undergoing abdominal aortic surgery. It may substantially alleviate shortages of allogenic blood and should be part of the armamentarium of vascular units.

Pseudo compartment syndrome of the calf in an athlete secondary to cystic adventitial disease of the popliteal artery.

We report a patient with calf pain induced by sport and exercise, initially thought to represent compartment syndrome, in whom MRI and duplex ultrasound ultimately revealed cystic adventitial disease of the popliteal artery. Surgical de-roofing of the popliteal artery resulted in complete resolution of symptoms with return to sporting activities.

Carotid artery angioplasty for restenosis following endarterectomy.

INTRODUCTION: The higher complication rate associated with the surgical treatment of restenosis following carotid endarterectomy (CEA) has led several authors to advocate angioplasty as the treatment of choice in the management of restenosis. We describe our experience with internal carotid artery angioplasty for post-endarterectomy restenosis over 7 years. PATIENTS AND METHODS: From January 1994 to April 2001, all patients with a >90% restenosis following CEA were considered for angioplasty. Thirty angioplasties were carried out in 25 patients, 80% (24/30), for asymptomatic recurrent stenosis. There was no difference between those who had intervention for recurrent stenosis (n=31) and those who did not (n=545) in age, sex, smoking status or incidence of diabetes or hypertension. A significantly greater number of patients who underwent angioplasty were hypercholesterolaemic (p<0.05, Chi-squared test). RESULTS: Mean time from surgery to angioplasty was 13 months (range 1-23). Angioplasty was technically successful in 29 cases (97%). Three patients (10%) experienced transient neurological symptoms during the procedure. There were no strokes. Ninety-six percent (28/29) of patients were followed up with duplex scanning. Mean follow-up was 20 months (range 2-48). Three patients developed a greater than 90% restenosis. CONCLUSION: Angioplasty is an acceptable alternative to surgery in the management of internal carotid artery restenosis following endarterectomy.

Exercise induced critical ischaemia of the upper limb secondary to a cervical rib.

The case is reported of a 32 year old woman with acute on chronic upper limb ischaemia due to thrombus from a cervical rib that had compressed the right subclavian artery of her dominant hand after use of a rowing machine. If not detected early, this condition can be debilitating especially in the young. A multidisciplinary approach is advisable to ensure a satisfactory outcome.

Vascular surgery of the upper limb: the first year of a new vascular service.

Upper limb vascular reconstruction represents a small part of the vascular surgical workload (5%). The aim of this study was to assess the incidence of upper limb vascular reconstruction in a Regional Hospital. During the first year of a new vascular surgical service in Waterford Regional Hospital, upper limb vascular problems were prospectively analysed. Upper limb vascular reconstruction comprised seven of the total 92 major vascular procedures performed. Three cases were emergencies and four elective. There was one case of penetrating injury, two injuries due to blunt trauma, three patients with thoracic outlet syndrome (TOS) and one chronic ischaemia. The male:female ratio was 4:3 and the mean age was 42 years. Six of the cases were arterial in nature only, and one was both venous and arterial. Two of the cases were associated with upper limb fractures and multiple trauma. Three patients had interposition reversed cephalic vein grafting. One patient had an embolectomy and endarterectomy. Procedures for TOS included excision of a cervical rib in two patients (one bilateral) and scalenectomy alone in one patient. Of these, one patient also had thrombolysis and thrombectomy of the axillary and brachial artery. All of the patients made a good functional recovery and all arteries remained patent but the patient with the brachial plexus injury is awaiting repair abroad. Upper limb vascular problems form a small but significant part (8%) of the workload. Many cases present as emergencies and maybe associated with multiple trauma. This emphasises the need for an emergency vascular surgery service in all trauma units.

Bisphosphonates in the treatment of Charcot neuroarthropathy: a double-blind randomised controlled trial.

AIMS/HYPOTHESIS: The management of charcot neuroarthropathy, a severe disabling condition in diabetic patients with peripheral neuropathy, is currently inadequate with no specific pharmacological treatment available. We undertook a double-blind randomised controlled trial to study the effect of pamidronate, a bisphosphonate, in the management of acute diabetic Charcot neuroarthropathy. METHODS: Altogether 39 diabetic patients with active Charcot neuroarthropathy from four centres in England were randomised in a double-blind placebo-controlled trial. Patients received a single infusion of 90 mg of pamidronate or placebo (saline). Foot temperatures, symptoms and markers of bone turnover (bone specific alkaline phosphatase and deoxypyridinoline crosslinks) were measured over the 12 months, in 10 visits. All patients also had standard treatment of the Charcot foot. RESULTS: Mean age of the study group (59 % Type II (non-insulin-dependent) diabetes mellitus) was 56.3 +/- 10.2 years. The mean temperature difference between active and control groups was 3.6 +/- 1.7 degrees C and 3.3 +/- 1.4 degrees C, respectively. There was a fall in temperature of the affected foot in both groups after 2 weeks with a further reduction in temperature in the active group at 4 weeks (active and placebo vs baseline; p = 0.001; p = 0.01, respectively), but no difference was seen between groups. An improvement in symptoms was seen in the active group compared with the placebo group (p < 0.001). Reduction in bone turnover (means +/- SEM) was greater in the active than in the control group. Urinary deoxypyridinoline in the pamidronate treated group fell to 4.4 +/- 0.4 nmol/mmol creatinine at 4 weeks compared with 7.1 +/- 1.0 in the placebo group (p = 0.01) and bone-specific alkaline phosphatase fell to 14.1 +/- 1.2 u/l compared with 18.6 +/- 1.6 u/l after 4 weeks, respectively (p = 0.03). CONCLUSION/INTERPRETATION: The bisphosphonate, pamidronate, given as a single dose leads to a reduction in bone turnover, symptoms and disease activity in diabetic patients with active Charcot neuroarthropathy.

Improving foot care for people with diabetes mellitus--a randomized controlled trial of an integrated care approach.

AIMS: To evaluate a model of integrated diabetic footcare, for identification and clinical management of the high risk diabetic foot, centred on the primary care-based diabetic annual review. METHODS: A pragmatic randomized controlled study was undertaken with matched cluster randomization of practices from 10 towns drawn from mid and east Devon responsible for the care of 1,939 people with diabetes (age > or =18 years). Outcome measures were patients' attitudes regarding the value and importance of footcare, patients' footcare knowledge, healthcare professionals' footcare knowledge and pattern of service utilization. RESULTS: Attitudes towards footcare improved in both intervention and control groups (mean percentage change 3.91, 0.68) with a significant difference in change of 3.18 (95% confidence interval (CI) 1.29-5.07) between the groups. Patients' knowledge about diabetic foot problems improved significantly in both groups (mean percentage change 1.09, 1.32) but with no significant difference in change: -0.09 (95% CI -1.81-1.63) between groups. Health professionals' knowledge scores improved in the intervention group (mean percentage change 13.2; P < 0.001). No improvement was seen in the control group (mean percentage change -0.2; P = 0.1) with a significant difference in change of 13.46 (95% CI 8.30-18.62) between groups. Appropriate referrals from intervention practices to the specialized foot clinic rose significantly (P = 0.05) compared with control practices (P = 0.14). CONCLUSIONS: Provision of integrated care arrangements for the diabetic foot has a positive impact on primary care staffs' knowledge and patients' attitudes resulting in an increased number of appropriate referrals to acute specialist services.

Should an appendix that looks 'normal' be removed at diagnostic laparoscopy for acute right iliac fossa pain?

OBJECTIVE: To find out whether the removal of the appendix from patients in whom laparoscopy for acute right iliac fossa pain shows no abnormality is justified to avoid the risk of missing acute appendicitis. PATIENTS: The records of patients who, between 1990 and 1997 had emergency laparoscopy for acute right iliac fossa pain were reviewed. Only those in whom laparoscopy had shown no abnormality and had not had the appendix removed were included in the study. METHODS: Outcome was assessed by telephone questionnaire to the patient, the general practitioner, or both. RESULTS: Emergency laparoscopy had been done for 254 patients. No abnormality was detected in 41. Full follow up was available on 34 patients (83%). 21 patients have remained entirely free of symptoms. Of the 13 patients who had recurrent symptoms, 2 subsequently had a histologically normal appendix removed, yet still had symptoms; 2 had a second laparoscopy that showed no abnormality; 5 had ultrasound; and 4 had colonoscopy or a barium enema examination. CONCLUSION: Removal of an appendix that looks 'normal' at emergency laparoscopy for right iliac fossa pain is unjustified.

Transgenic human lambda 5 rescues the murine lambda 5 nullizygous phenotype.

The human lambda 5 (hu lambda 5) gene is the structural homologue of the murine lambda 5 (m lambda 5) gene and is transcriptionally active in pro-B and pre-B lymphocytes. The lambda 5 and VpreB polypeptides together with the Ig mu H chain and the signal-transducing subunits, Ig alpha and Ig beta, comprise the pre-B cell receptor. To further investigate the pro-B/pre-B-specific transcription regulation of hu lambda 5 in an in vivo model, we generated mouse lines that contain a 28-kb genomic fragment encompassing the entire hu lambda 5 gene. High levels of expression of the transgenic hu lambda 5 gene were detected in bone marrow pro-B and pre-B cells at the mRNA and protein levels, suggesting that the 28-kb transgene fragment contains all the transcriptional elements necessary for the stage-specific B progenitor expression of hu lambda 5. Flow cytometric and immunoprecipitation analyses of bone marrow cells and Abelson murine leukemia virus-transformed pre-B cell lines revealed the hu lambda 5 polypeptide on the cell surface and in association with mouse Ig mu and mouse VpreB. Finally, we found that the hu lambda 5 transgene is able to rescue the pre-B lymphocyte block when bred onto the m lambda 5-/- background. Therefore, we conclude that the hu lambda 5 polypeptide can biochemically and functionally substitute for m lambda 5 in vivo in pre-B lymphocyte differentiation and proliferation. These studies on the mouse and human pre-B cell receptor provide a model system to investigate some of the molecular requirements necessary for B cell development.

Identification of an immunodominant ABC transporter in methicillin-resistant Staphylococcus aureus infections.

Immunoblotting sera from 26 patients with septicemia due to an epidemic strain of methicillin-resistant Staphylococcus aureus (EMRSA-15), 6 of whom died, revealed an immunodominant EMRSA-15 antigen at 61 kDa. There was a statistically significant correlate (P < 0.001) between survival and immunoglobulin G to the 61-kDa band. The antigen was identified by sequencing positive clones obtained by screening a genomic expression library of EMRSA-15 with pooled sera from patients taken after the septicemic episode. Eluted antibody reacted with the 61-kDa antigen on immunoblots. The amino terminus was obtained by searching the S. aureus NCTC 8325 and MRSA strain COL databases, and the whole protein was expressed in Escherichia coli TOP 10F'. The derived amino acid sequence showed homology with ABC transporters, with paired Walker A and Walker B motifs and 73% homology to YkpA from Bacillus subtilis. Epitope mapping of the derived amino acid sequence with sera from patients who had recovered from EMRSA-15 septicemia delineated seven epitopes. Three of these epitopes, represented by peptides 1 (KIKVYVGNYDFWYQS), 2 (TVIVVSHDRHFLYNNV), and 3 (TETFLRGFLGRMLFS), were synthesized and used to isolate human recombinant antibodies from a phage antibody display library. Recombinant antibodies against peptides 1 and 2 gave logarithmic reductions in organ colony counts, compared with control groups, in a mouse model of the infection. This study suggests the potential role of an ABC transporter as a target for immunotherapy.

Intermolecular hydrogen bonding of the two independent molecules of N-3,5-dinitrobenzoyl-L-leucine.

The title compound, C(13)H(15)N(3)O(7), crystallizes as two independent molecules which differ in their conformation. Intermolecular hydrogen bonding between the amide and carboxylic acid groups as N-H.O=C interactions results in the formation of one-dimensional chains with N.O distances of 2.967 (6) and 3.019 (6) A. Neighbouring chains are linked by C=O.H-O interactions to form a two-dimensional network, with O.O distances of 2.675 (6) and 2.778 (6) A.