“The chimney graft”—A simple technique for endovascular repair of complex juxtarenal abdominal aortic aneurysms in no‐option patients

Endovascular aneurysm repair (EVAR) has developed as a less invasive alternative to open surgery for patients with abdominal aortic aneurysms. However, patients with very short infrarenal necks require complex surgical open repair, which is associated with increased mortality and morbidity. The risk of complex open repair may be prohibitive in high‐risk patients. Thus, modifying the technique of EVAR may be required in such patients to successfully exclude aneurysms. An alternative that can be used in these patients is the so‐called “chimney graft” technique. We report two cases where the chimney graft technique was used with good immediate results. © 2010 Wiley‐Liss, Inc.     

Divergent roles of sphingosine kinases in kidney ischemia-reperfusion injury

Sphingosine-1-phosphate (S1P), produced by sphingosine kinase 1 (SphK1) or kinase 2 (SphK2), mediates biological effects through intracellular and/or extracellular mechanisms. Here we determined a role for these kinases in kidney injury of wild-type mice following ischemia-reperfusion. SphK1 but not SphK2 mRNA expression and activity increased in the kidney following injury relative to sham-operated animals. Although SphK1(-/-) mice had no alteration in renal function following injury, mice with a disrupted SphK2 gene (SphK2(tr/tr)) had histological damage and impaired function. The immune-modulating pro-drug, FTY720, an S1P agonist failed to provide protection in SphK2(tr/tr) mice. Injured kidneys of these mice showed increased neutrophil infiltration and neutrophil chemokine expression along with a 3- to 5-fold increase in expression of the G-protein-coupled receptor S1P(3) compared to heterozygous SphK2(+/tr) mice. Kidney function and reduced vascular permeability were preserved in S1P(3)(-/-) compared to S1P(3)(+/-) mice after ischemia-reperfusion injury, suggesting increased S1P(3) mRNA may play a role in the injury of SphK2(tr/tr) mice. Our study suggests that constitutive expression of SphK2 may contribute to reduced ischemia-reperfusion injury of the kidney, and its absence may enhance injury due to increased neutrophil infiltration and S1P(3) activation. We also confirm that SphK2 is necessary to mediate the protective effects of FTY720.     

Serum Serotonin Abnormality in Depression

Background

Serotonin plays an important role in treatment of depression. We evaluated the clinical correlates of plasma serotonin levels in depressed patients before and after treatment.

Methods

Study sample comprised of 40 patients diagnosed on ICD-10 diagnostic criteria, and an equal number of healthy matched controls. Subjects were evaluated on Beck''s Depression Inventory (BDI) and Suicide Ideation Scale (SIS), before and after the treatment. Blood samples were collected from all the cases and controls before starting the antidepressant medication with selective serotonin reuptake inhibitors (SSRI''s). Serum serotonin levels were measured before and after treatment.

Result

Significant differences in scores before and after the intervention on BDI, SIS and serotonin levels of cases and controls (p<.000) were noted. Correlation between the serum serotonin levels before and after the treatment, and between the rating scales did not reveal significant association (p > 0.05). Patients with suicidal intentions had lower levels of serotonin. The scores changed after intervention.

Conclusion

Treatment with SSRI''s had shown significant changes in clinical conditions. However these changes did not relate significantly with serum serotonin levels.Key Words: Serotonin, Depression, Selective serotonin reuptake inhibitors     

A conserved role for Hox paralog group 4 in regulation of hematopoietic progenitors

Regulatory circuits that control stem cell fate decisions can be identified and understood by manipulating individual regulatory elements genetically. While impractical in the rare somatic stem cells of primary tissue, this approach is feasible in embryonic stem cells differentiated in vitro into the somatic stem cell type of interest. We present an improved highly efficient targeting system allowing genes to be integrated into a predetermined, doxycycline-inducible locus, and corresponding inducible embryonic stem cell lines to be generated rapidly. We apply this system to evaluate a key hematopoietic progenitor cell regulatory element, HoxB4, and its mammalian paralogs, whose effects have not yet been tested in this context. We show that all Hox paralog group 4 members, A4, B4, C4, and D4, have similar effects on hematopoietic stem and progenitor self-renewal in vitro, and thus classify Hox paralog group 4 as promoting self-renewal. Each paralog group 4 member both promotes proliferation and inhibits differentiation, enabling the exponential expansion of hematopoietic progenitors from the c-kit(+)/CD41(+) cell fraction of day 6 murine embryoid bodies. By evaluating a set of deletion mutants we show that sequences in addition to the homeodomain and hexapeptide motif are required for this activity. These results highlight the utility of this expression system to perform functional and structural analyses of genetic regulators of cell fate decisions.     

Validation of MCADD newborn screening

Medium‐chain acyl‐CoA dehydrogenase deficiency (MCADD) represents a potentially fatal fatty acid β‐oxidation disorder. Newborn screening (NBS) by tandem mass spectrometry (MS/MS) has been implemented worldwide, but is associated with unresolved questions regarding population heterogeneity, burden on healthy carriers, cut‐off policies, false‐positive and negative rates. In a retrospective case‐control study, 333 NBS samples showing borderline acylcarnitine patterns but not reaching recall criteria were genotyped for the two most common mutations (c.985A>G/c.199C>T) and compared with genotypes and acylcarnitines of 333 controls, 68 false‐positives, and 34 patients. c.985A>G was more frequently identified in the study group and false‐positives compared to controls (1:4.3/1:2.3 vs. 1:42), whereas c.199C>T was found more frequently only within the false‐positives (1:23). Biochemical criteria were devised to differentiate homozygous (c.985A>G), compound heterozygous (c.985A>G/c.199C>T), and heterozygous individuals. Four false‐negatives were identified because our initial algorithm required an elevation of octanoylcarnitine (C₈) and three secondary markers in the initial and follow‐up sample. The new approach allowed a reduction of false‐positives (by defining high cut‐offs: 1.4 μmol/l for C₈; 7 for C₈/C₁₂) and false‐negatives (by sequencing the ACADM gene of few suspicious samples). Our validation strategy is able to differentiate healthy carriers from patients doubling the positive predictive value (42→88%) and to target NBS to MCADD‐subsets with potentially higher risk of adverse outcome. It remains controversial, if NBS programs should aim at identifying all subsets of all diseases included. Because the natural course of milder variants cannot be assessed by observational studies, our strategy could serve as a general model for evaluation of MS/MS‐based NBS.     

Italian healthcare workers' views on mandatory vaccination

Background  

Mandatory vaccination has contributed to the success of immunisation programmes but voluntary vaccination allows people to be responsible for their own health. There are benefits from both policies and the arguments between them remain subject to debate within and without the scientific community, both nationally and internationally. The aim of this study is to assess the opinions of those who actually work in the Vaccination Service.     

Paroxysmal atrial fibrillation in critically ill patients with sepsis

The objective of this retrospective cohort study was to describe the incidence of paroxysmal atrial fibrillation and to determine its risk factors and effect on outcome in critically ill patients with sepsis. The study included 81 patients with sepsis admitted to an intensive care unit. In all, 25 patients (31%) developed paroxysmal atrial fibrillation. Advanced age, history of paroxysmal atrial fibrillation, higher severity of illness at intensive care unit admission, and lower left ventricular ejection fraction were risk factors for paroxysmal atrial fibrillation. Multiple logistic regression analysis showed that paroxysmal atrial fibrillation was independently associated with 28-day mortality (odds ratio = 3.284; 95% confidence interval, 1.126-9.574). The incidence of paroxysmal atrial fibrillation is high in critically ill patients with sepsis. It occurs more frequently in patients with advanced age, history of paroxysmal atrial fibrillation, high severity of illness, and lower left ventricular ejection fraction and is associated with increased mortality.     

What is mechanical back pain and how best to treat it?

Back pain is one of the most common patient complaints brought forth to physicians. Mechanical back pain accounts for 97% of cases, arising from spinal structures such as bone, ligaments, discs, joints, nerves, and meninges. Acute back pain in the absence of progressive neurologic deficits and other underlying nonmechanical causes may be treated conservatively, with specific emphasis on maintaining activity levels and function. Mechanical back pain persisting for more than 4 to 6 weeks may warrant further diagnostic testing and imaging. Common causes of mechanical back pain include spinal stenosis, herniated discs, zygapophysial joint pain, discogenic pain, vertebral fractures, sacroiliac joint pain, and myofascial pain. A wide variety of treatments are available, with different treatments specifically targeted toward different causes. A balanced approach, which takes into account patient psychosocial factors and incorporates multidisciplinary care, increases the likelihood of success from back pain interventions.     

Developing a community facilitator‐led participatory learning and action women's group intervention to improve infant feeding,care and dental hygiene practices in South Asian infants: NEON programme

IntroductionThe Nurture Early for Optimal Nutrition (NEON) study is a multiphase project that aims to optimize feeding, care and dental hygiene practices in South Asian children <2 years in East London, United Kingdom. The multiphase project uses a participatory learning and action (PLA) approach facilitated by a multilingual community facilitator. In this paper, we elaborate on the process and results of the Intervention Development Phase in the context of the wider NEON programme.MethodsQualitative community‐based participatory intervention codevelopment and adaptation.SettingCommunity centres in East London and online (Zoom) meetings and workshops.ParticipantsIn total, 32 participants registered to participate in the Intervention Development Phase. Four Intervention Development workshops were held, attended by 25, 17, 20 and 20 participants, respectively.ResultsCollaboratively, a culturally sensitive NEON intervention package was developed consisting of (1) PLA group facilitator manual, (2) picture cards detailing recommended and nonrecommended feeding, care and dental hygiene practices with facilitators/barriers to uptake as well as solutions to address these, (3) healthy infant cultural recipes, (4) participatory Community Asset Maps and (5) list of resources and services supporting infant feeding, care and dental hygiene practices.ConclusionThe Intervention Development Phase of the NEON programme demonstrates the value of a collaborative approach between researchers, community facilitators and the target population when developing public health interventions. We recommend that interventions to promote infant feeding, care and dental hygiene practices should be codeveloped with communities. Recognizing and taking into account both social and cultural norms may be of particular value for infants from ethnically diverse communities to develop interventions that are both effective in and accepted by these communities.Patient and Public Involvement and EngagementConsiderable efforts were placed on Patient/Participant and Public Involvement and Engagement. Five community facilitators were identified, each of which represented one ethnic/language group: (i) Bangladeshi/Bengali and Sylheti, (ii) Pakistani/Urdu, (iii) Indian/Gujrati, (iv) Indian/Punjabi and (v) Sri Lankan/Tamil. The community facilitators were engaged in every step of the study, from the initial drafting of the protocol and study design to the Intervention Development and refinement of the NEON toolkit, as well as the publication and dissemination of the study findings. More specifically, their role in the Intervention Development Phase of the NEON programme was to:

• 1.Support the development of the study protocol, information sheets and ethics application.
• 2.Ensure any documents intended for community members are clear, appropriate and sensitively worded.
• 3.Develop strategies to troubleshoot any logistical challenges of project delivery, for example, recruitment shortfalls.
• 4.Contribute to the writing of academic papers, in particular reviewing and revising drafts.
• 5.Develop plain language summaries and assist in dissemination activities, for example, updates on relevant websites.
• 6.Contribute to the development of the NEON intervention toolkit and recruitment of the community members.
• 7.Attend and contribute to Intervention Development workshops, ensuring the participant''s voices were the focus of the discussion and workshop outcomes.