Neuroprotective signaling pathways are modulated by adenosine in the anoxia tolerant turtle

Cumulative evidence shows a protective role for adenosine A1 receptors (A1R) in hypoxia/ischemia; A1R stimulation reduces neuronal damage, whereas blockade exacerbates damage. The signal transduction pathways may involve the mitogen-activated protein kinase (MAPK) pathways and serine/threonine kinase (AKT), with cell survival depending on the timing and degree of upregulation of these cascades as well as the balance between pro-survival and pro-death pathways. Here, we show in vitro that extracellular signal-regulated kinase (ERK1/2) and phosphatidylinositol 3-kinase (PI3-K/AKT) activation is dependent on A1R stimulation, with further downstream effects that promote neuronal survival. Phosphorylated ERK1/2 (p-ERK) and AKT (p-AKT) as well as Bcl-2 are upregulated in anoxic neuronally enriched primary cultures from turtle brain. This native upregulation is further increased by the selective A1R agonist 2-chloro-N-cyclopentyladenosine (CCPA), whereas the selective antagonist 8-cyclopentyl-1,3-dihydropylxanthine (DPCPX) decreases p-ERK and p-AKT expression. Conversely, A1R antagonism resulted in increases in phosphorylated JNK (p-JNK), p38 (p-p38), and Bax. As pathological and adaptive changes occur simultaneously during anoxia/ischemia in mammalian neurons, the turtle provides an alternative model to analyze protective mechanisms in the absence of evident pathologies.     

Developing a culture of nursing research through clinical-academic partnership

Evidence based practice is essential to advanced practice nursing, enabling the delivery of quality care and improved patient outcomes. As the name suggests, it requires healthcare decisions to be based on the best available and current evidence. Advanced practice nurses need astute critical analysis skills to appraise the evolving literature, and require research skills to lead on scientific inquiry and develop the profession. Yet, advanced practice nurses may not recognize themselves as research leaders. Participation in a journal club can promote evidence-based practice, improve clinician's critical thinking skills, and expose members to different research methodologies, however, nurses continue to face barriers to participation in these clubs. Establishing a clinical-academic partnership appears to be both mutually beneficial for clinicians and academics and is a significant enabler in the sustainability and functioning of the club through sharing expertise and experience. A supportive workplace culture is favourable to research utilization and knowledge translation. This paper outlines the role, practicalities, challenges, and benefits of setting up a hybrid urology journal and research club for advanced practice nurses in a clinical-academic partnership.     

Oliguric and non-oliguric acute renal failure in malaria in west zone of rajasthan,India-A comparative study

ObjectiveTo report a comparative clinical and histopathological study on oliguric and non-oliguric acute renal failure (ARF) in malaria.Method311 consecutive cases of malaria out of which 74 (23.79%) had ARF as per WHO criteria were conducted. Mean age was 32.58 (range 15–60 years) and male: female was 2:1.ResultMost of the cases developed ARF within 10 d of onset. 18 cases (11 falciparum, 2 mixed, 5 vivax) presented with oliguric and 56 (41 falciparum, 6 mixed, 9 vivax) with non-oliguric renal failure. Associated major manifestations were jaundice (75.68%), cerebral malaria (41.89%), bleeding manifestations (32.43%), severe anemia (27.03%), hypotension (25.68%), multi-organ failure (18.92%), severe thrombocytopenia (12.16%), and ARDS (8.11%). Kidney biopsy (n=20) showed acute tubular necrosis (n=7), Mesangioproliferative glomerulonephritis (n=4) or both (n=9). Hemodialysis was done in 8 cases of oliguric renal failure out of which 4 survived (average no. of session 2.9).ConclusionMost of the cases recovered within 3 weeks. Total mortality was 28.38% (n=21) and mortality was more in oliguric renal failure (72.22%) as compare to non-oliguric renal failure (14.29%).     

PR interval prolongation is significantly associated with aortic root abscess: An age‐ and gender‐matched study

BackgroundElectrocardiographic abnormalities, such as PR interval prolongation, have been anecdotally reported in patients with aortic root abscess (ARA). An electrocardiographic marker may be useful in identifying those patients with aortic valve endocarditis who may progress to ARA. The objective of this study is to evaluate the change in the PR interval in patients with surgically confirmed ARA and compare it to age‐ and gender‐matched controls with echocardiographically or surgically confirmed aortic valve endocarditis but without aortic root abscess and those hospitalized with diagnoses other than endocarditis.MethodsPatients were eligible for enrollment if they were 18 years or older and were hospitalized for either ARA, aortic valve endocarditis, or for unrelated reasons and had at least one 12‐lead electrocardiogram (ECG) prior to or on the day of hospitalization and at least one ECG after hospitalization but prior to any cardiac surgical procedure. Delta PR interval, defined as the difference between the pre‐ and post‐admission PR interval, was the primary outcome of interest. The patients in the ARA group were age‐ and gender‐matched to patients with aortic valve endocarditis and to those without endocarditis. Comparisons of demographic variables and study outcomes were performed.ResultsEighteen patients with surgically confirmed ARA were enrolled. These patients were age‐ and gender‐matched to 19 patients with aortic valve endocarditis and 18 patients with no past history or evidence of endocarditis during hospitalization. No difference was noted in the baseline PR interval between the groups. However, the PR interval following admission in the aortic root abscess group (201 ± 66 ms) was significantly longer than the PR interval in both the aortic valve endocarditis (162 ± 27 ms) (24%, p = .009) and no endocarditis (143 ± 24 ms) (40%, p < .001) groups. The primary outcome measure, delta PR interval, was significantly longer in the ARA group (35 ± 51 ms) than no endocarditis (−5 ± 17 ms) (p = .001) and aortic valve endocarditis groups (0.2 ± 18) (p = .003).ConclusionsThe findings of our study support the notion that the PR interval is more likely to be prolonged in patients with ARA. Since ARA is associated with a high morbidity and mortality, PR interval prolongation in a patient with aortic valve endocarditis should prompt a thorough evaluation for aortic root involvement.     

Advances in the SUI Surgeries

Stress urinary incontinence is a condition associated with advancing age and high parity. Millions of women all over the world have suffered, in silence, embarrassment and social isolation due to this condition. Over the years, several operative procedures have evolved for correction of urinary incontinence with many of them having poor success or high recurrence rates over long-term period. This mini review covers various surgical procedures evolved over the last couple of years and recent advances in the management of urinary incontinence.     

Portable lead analyzer to locate source of lead

Objective :To investigate the sources of lead in the environment in children with elevated blood, with the help of a Field Portable X-Ray Fluorescence Analyzer.Methods : One hundred and seven school children were chosen for this study on a random basis, from Mangalore and Karnataka. Their blood lead was analyzed. Of the cases analyzed, 10 students whose blood lead level was more than 40 μg/dl were investigated using a field portable X-Ray Fluorescence Analyzer. This is the first time such a device has been available for this purpose in India.Results: The ‘likely’ source of lead exposure could be determined in eight cases which was from the immediate environment of the children like ‘lead-based’ paint on surfaces in the house, on playground and other exterior equipment; lead storage batteries, contaminated dust and soil and other lead-containing substances.Conclusion: The use of an X-Ray Fluorescence Analyser appeared to be useful in determining the source of lead     

Prevention and management of food allergy

The phenotypic expression and natural history of food allergy vary widely according to the patient's age, disease presentation and type of offending food. Prevention of food allergy might be achieved by altering the dietary factors responsible for the sensitization and phenotypic expression of the disease. Owing to the peculiarity of the atopic status, a minute amount of allergens can trigger both sensitization and symptoms in atopic individuals. The oral dose of β-lactoglobulin causing sensitization can be estimated to be between 1 ng and several milligrams. In food allergy, sensitization and treatment are allergen specific; therefore, for primary prevention (avoiding sensitization) and secondary prevention of food allergy (avoiding symptoms in an already sensitized subject), a product without immunogenic and allergenic epitopes should be given in each case. Babies of atopic parents are particularly prone to develop food allergy and for this reason they are called high-risk babies. Cow's milk is the most commonly offending food in both gastrointestinal and cutaneous manifestations. Cow's milk proteins are potent allergens and around 2.5% of infants experience cow's milk allergy in the first years of life. The major risk factors for cow's milk allergy are positive family history of atopy and early exposure to cow's milk proteins. Hydrolysate formulae have been developed for the purpose of reducing the allergenicity of cow's milk proteins. More recently, partially and extensively hydrolysed formulae have also been used for feeding babies with a high risk of atopy for the prevention of cow's milk allergy. However, according to the results of a recent randomized controlled study, only an extensively hydrolysated formula, and not a partially hydrolysated formula, significantly decreased the prevalence of cow's milk allergy.     

What does fetal autopsy unmask in oligohydramnios?

Objective: We aimed to determine the value of autopsy in fetuses with antenatally diagnosed oligohydramnios.

Patients and methods: We evaluated all fetal losses over a period of 6.5 years. Those with oligohydramnios on antenatal scan were critically analyzed. Oligohydramnios was defined as amniotic fluid index of less than five objectively or as an obvious lack of liquor at subjective assessment. A detailed postmortem examination was carried out in all the fetuses after obtaining an informed consent.

Results: Fetal autopsy was conducted in 255 cases. Fifty-five (21.5%) fetuses were diagnosed to have oligohydramnios on antenatal ultrasonography. On analysis of antenatal causes of oligohydramnios, maternal/placental factors were noted in 18%, ultrasound findings known to affect amniotic fluid in 27% while cause remained unidentified in 54.5% of cases. On autopsy, fetal malformations were noted in 61.8% cases, intrauterine growth retardation in 21.8% fetuses and no obvious malformations in 16.3% fetuses. Renal anomalies were noted in 40% cases and non-renal malformations in 21.8% cases.

Conclusion: The postmortem examination helped us to identify the cause of fetal loss in 46 (83.6%) fetuses with antenatal oligohydramnios. A working diagnosis could not have been established without autopsy in 19 (34.5%) cases.     

High‐frequency ventilation with the Dräger Babylog 8000plus: measuring the delivered frequency

Background: Ventilator frequency is one of the determinants of tidal volume delivery during high‐frequency ventilation. Clinicians increasingly use data on ventilator displays to inform their decisions. Aim: To measure the frequencies delivered by the Dräger Babylog 8000plus ventilator when used in high‐frequency mode. Methods: Ventilator waveforms using a test lung were recorded at the full range of settings 5–20 Hz using Spectra software at 1000 Hz. The changes in frequency produced by a 1‐ Hz change in set frequency were calculated. Actual and displayed frequencies were compared. Results: For settings up to 12 Hz, median (range) difference between set and delivered frequencies was 0 (?0.4 to +0.1) Hz. Above 12 Hz, delivered frequency varied by ?0.3 (?1.9 to +0.3) Hz. For 1‐ Hz changes in frequency settings, in the range 5–12 Hz, 1‐ Hz changes produced a change in delivered frequency of 1.0 (0.6–1.4) Hz. Above 12 Hz, the corresponding changes were 0.7 (0–2.9) Hz. The ventilator displays the set frequency during operation rather than the delivered frequency. Conclusion: At 12 Hz and below, the differences between set and delivered frequencies were relatively small compared with those at 13 Hz and higher. Above 13 Hz, the difference between set and delivered frequencies was up to 2.9 Hz. Some frequency setting changes did not result in a change in delivered frequency.     

Cytotoxic T cell epitope in cattle from the attachment glycoproteins of rinderpest and peste des petits ruminants viruses

The surface glycoproteins of rinderpest virus (RPV) confer protective immunity in cattle. We demonstrated that cattle immunized with a recombinant extracellular baculovirus expressing the hemagglutinin (H) protein of RPV (rECV-H) generate virus neutralizing antibody responses, bovine leukocyte antigen (BoLA) class II restricted helper T cell responses and BoLA class I restricted cytotoxic T cell (CTL) responses against RPV-H and hemagglutinin-neuraminidase (HN) glycoprotein of closely related Peste des petits ruminants virus (PPRV). In this study, employing autologous skin fibroblasts transiently expressing truncations of H and HN in a BoLA class I restricted lymphoproliferation assay, we have mapped a highly homologous domain (amino acids 400-423) on these proteins harboring a CTL epitope. Subsequently, based on sequence comparison with available BoLA class I binding motifs, we have identified a BoLA-A11 binding motif (amino acids 408-416) in the stimulatory domain. Autologous cells pulsed with a synthetic peptide corresponding to this sequence stimulated CTLs from rECV-H immunized as well as tissue culture attenuated RPV vaccinated cattle of different breeds and parentage. This is the first epitope identified in cattle on the attachment glycoproteins of RPV and PPRV.