A Review of the Design Process for Implantable Orthopedic Medical Devices

The design process for medical devices is highly regulated to ensure the safety of patients. This paper will present a review of the design process for implantable orthopedic medical devices. It will cover the main stages of feasibility, design reviews, design, design verification, manufacture, design validation, design transfer and design changes

Convective burn from use of hairdryer for heel warming prior to the heel prick test - a case report

Background Blood sampling through heel lancing is the most common invasive painful procedure performed on newborn infants. Case Presentation We report the case of a five day old infant who sustained burns to the left foot and leg after the mother's hairdryer was used by the midwife to warm the baby's heel prior to capillary blood sampling (CBS) with an automated device. Conclusion Heel warming is not recommended for routine CBS although it is often practiced. If pre-warming is to be practiced, standardised devices should be used rather than improvised techniques. This will reduce the risk of injury to these infants

Truncated and Helix-Constrained Peptides with High Affinity and Specificity for the cFos Coiled-Coil of AP-1

Protein-based therapeutics feature large interacting surfaces. Protein folding endows structural stability to localised surface epitopes, imparting high affinity and target specificity upon interactions with binding partners. However, short synthetic peptides with sequences corresponding to such protein epitopes are unstructured in water and promiscuously bind to proteins with low affinity and specificity. Here we combine structural stability and target specificity of proteins, with low cost and rapid synthesis of small molecules, towards meeting the significant challenge of binding coiled coil proteins in transcriptional regulation. By iteratively truncating a Jun-based peptide from 37 to 22 residues, strategically incorporating i-->i+4 helix-inducing constraints, and positioning unnatural amino acids, we have produced short, water-stable, alpha-helical peptides that bind cFos. A three-dimensional NMR-derived structure for one peptide (24) confirmed a highly stable alpha-helix which was resistant to proteolytic degradation in serum. These short structured peptides are entropically pre-organized for binding with high affinity and specificity to cFos, a key component of the oncogenic transcriptional regulator Activator Protein-1 (AP-1). They competitively antagonized the cJun–cFos coiled-coil interaction. Truncating a Jun-based peptide from 37 to 22 residues decreased the binding enthalpy for cJun by ~9 kcal/mol, but this was compensated by increased conformational entropy (TDS ≤ 7.5 kcal/mol). This study demonstrates that rational design of short peptides constrained by alpha-helical cyclic pentapeptide modules is able to retain parental high helicity, as well as high affinity and specificity for cFos. These are important steps towards small antagonists of the cJun-cFos interaction that mediates gene transcription in cancer and inflammatory diseases

Migraine aura: retracting particle-like waves in weakly susceptible cortex

Cortical spreading depression (SD) has been suggested to underlie migraine aura. Despite a precise match in speed, the spatio-temporal patterns of SD and aura symptoms on the cortical surface ordinarily differ in aspects of size and shape. We show that this mismatch is reconciled by utilizing that both pattern types bifurcate from an instability point of generic reaction-diffusion models. To classify these spatio-temporal pattern we suggest a susceptibility scale having the value [sigma]=1 at the instability point. We predict that human cortex is only weakly susceptible to SD ([sigma]<1), and support this prediction by directly matching visual aura symptoms with anatomical landmarks using fMRI retinotopic mapping. We discuss the increased dynamical repertoire of cortical tissue close to [sigma]=1, in particular, the resulting implications on migraine pharmacology that is hitherto tested in the regime ([sigma]>>1), and potentially silent aura occurring below a second bifurcation point at [sigma]=0 on the susceptible scale

Fusion between Leishmania amazonensis and Leishmania major Parasitophorous Vacuoles: Live Imaging of Coinfected Macrophages

Protozoan parasites of the genus Leishmania alternate between flagellated, elongated extracellular promastigotes found in insect vectors, and round-shaped amastigotes enclosed in phagolysosome-like Parasitophorous Vacuoles (PVs) of infected mammalian host cells. Leishmania amazonensis amastigotes occupy large PVs which may contain many parasites; in contrast, single amastigotes of Leishmania major lodge in small, tight PVs, which undergo fission as parasites divide. To determine if PVs of these Leishmania species can fuse with each other, mouse macrophages in culture were infected with non-fluorescent L. amazonensis amastigotes and, 48 h later, superinfected with fluorescent L. major amastigotes or promastigotes. Fusion was investigated by time-lapse image acquisition of living cells and inferred from the colocalization of parasites of the two species in the same PVs. Survival, multiplication and differentiation of parasites that did or did not share the same vacuoles were also investigated. Fusion of PVs containing L. amazonensis and L. major amastigotes was not found. However, PVs containing L. major promastigotes did fuse with pre-established L. amazonensis PVs. In these chimeric vacuoles, L. major promastigotes remained motile and multiplied, but did not differentiate into amastigotes. In contrast, in doubly infected cells, within their own, unfused PVs metacyclic-enriched L. major promastigotes, but not log phase promastigotes - which were destroyed - differentiated into proliferating amastigotes. The results indicate that PVs, presumably customized by L. major amastigotes or promastigotes, differ in their ability to fuse with L. amazonensis PVs. Additionally, a species-specific PV was required for L. major destruction or differentiation – a requirement for which mechanisms remain unknown. The observations reported in this paper should be useful in further studies of the interactions between PVs to different species of Leishmania parasites, and of the mechanisms involved in the recognition and fusion of PVs

Rising statin use and effect on ischemic stroke outcome

BACKGROUND: Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) have neuroprotective effects in experimental stroke models and are commonly prescribed in clinical practice. The aim of this study was to determine if patients taking statins before hospital admission for stroke had an improved clinical outcome. METHODS: This was an observational study of 436 patients admitted to the National Institutes of Health Suburban Hospital Stroke Program between July 2000 and December 2002. Self-reported risk factors for stroke were obtained on admission. Stroke severity was determined by the admission National Institutes of Health Stroke Scale score. Good outcome was defined as a Rankin score < 2 at discharge. Statistical analyses used univariate and multivariate logistic regression models. RESULTS: There were 436 patients with a final diagnosis of ischemic stroke; statin data were available for 433 of them. A total of 95/433 (22%) of patients were taking a statin when they were admitted, rising from 16% in 2000 to 26% in 2002. Fifty-one percent of patients taking statins had a good outcome compared to 38% of patients not taking statins (p = 0.03). After adjustment for confounding factors, statin pretreatment was associated with a 2.9 odds (95% CI: 1.2–6.7) of a good outcome at the time of hospital discharge. CONCLUSIONS: The proportion of patients taking statins when they are admitted with stroke is rising rapidly. Statin pretreatment was significantly associated with an improved functional outcome at discharge. This finding could support the early initiation of statin therapy after stroke

Measurement of Exclusive B Decays to Final States Containing a Charmed Baryon

Using data collected by the CLEO detector in the Upsilon(4S) region, we report new measurements of the exclusive decays of B mesons into final states of the type Lambda_c^+ p-bar n(pi), where n=0,1,2,3. We find signals in modes with one, two and three pions and an upper limit for the two body decay Lambda_c^+ pbar. We also make the first measurements of exclusive decays of B mesons to Sigma_c p-bar n(pi), where n=0,1,2. We find signals in modes with one and two pions and an upper limit for the two body decay Sigma_c p-bar. Measurements of these modes shed light on the mechanisms involved in B decays to baryons.Comment: 11 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, submitted to PR

Measurement of the Masses and Widths of the Sigma_c^++ and Sigma_c^0 Charmed Baryons

Using data recorded by the CLEO II and CLEO II.V detector configurations at CESR, we report new measurements of the masses of the Sigma_c^{++} and Sigma_c^0 charmed baryons, and the first measurements of their intrinsic widths. We find M(Sigma_c^{++}) - M(Lambda_c^+) = 167.4 +- 0.1 +- 0.2 MeV, Gamma(Sigma_c^{++}) = 2.3 +- 0.2 +- 0.3 MeV, and M(Sigma_c^0) - M(Lambda_c^+) = 167.2 +- 0.1 +- 0.2 MeV, Gamma(Sigma_c^0) = 2.5 +- 0.2 +- 0.3 MeV, where the uncertainties are statistical and systematic, respectively.Comment: 9 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, submitted to PRD, Rapid Communications. Reference [13] correcte

Adherence with statins in a real-life setting is better when associated cardiovascular risk factors increase: a cohort study

<p>Abstract</p> <p>Background</p> <p>While the factors for poor adherence for treatment with statins have been highlighted, the impact of their combination on adherence is not clear.</p> <p>Aims</p> <p>To estimate adherence for statins and whether it differs according to the number of cardiovascular risk factors.</p> <p>Methods</p> <p>A cohort study was conducted using data from the main French national health insurance system reimbursement database. Newly treated patients with statins between September 1 and December 31, 2004 were included. Patients were followed up 15 months. The cohort was split into three groups according to their number of additional cardiovascular risk factors that included age and gender, diabetes mellitus and cardiovascular disease (using co-medications as a <it>proxy</it>). Adherence was assessed for each group by using four parameters: <it>(i) </it>proportion of days covered by statins, <it>(ii) </it>regularity of the treatment over time, <it>(iii) </it>persistence, and <it>(iv) </it>the refill delay.</p> <p>Results</p> <p>16,397 newly treated patients were identified. Of these statin users, 21.7% did not have additional cardiovascular risk factors. Thirty-one percent had two cardiovascular risk factors and 47% had at least three risk factors. All the parameters showed a sub-optimal adherence whatever the group: days covered ranged from 56% to 72%, regularity ranged from 23% to 33% and persistence ranged from 44% to 59%, but adherence was better for those with a higher number of cardiovascular risk factors.</p> <p>Conclusions</p> <p>The results confirm that long-term drug treatments are a difficult challenge, particularly in patients at lower risk and invite to the development of therapeutic education.</p

Observation of Exclusive barB --> D(*) K*- Decays

We report the first observation of the exclusive decays \bar B\to D^{(*)}K^{*-}, using 9.66 x 10^{6} B\bar{B} pairs collected at the \Upsilon(4S) with the CLEO detector. We measure the following branching fractions: {\cal B}(B^- -> D^0 K^{*-})=(6.1 +- 1.6 +-1.7)x10^{-4}, {\cal B}(\bar{B^0} -> D^+K^{*-})=(3.7 +- 1.5 +- 1.0) x 10^{-4}, {\cal B}(\bar{B^0} -> D^{*+}K^{*-})=(3.8 +- 1.3 +- 0.8) x 10^{-4} and {\cal B}(B^- --> D^{*0} K^{*-})=(7.7 +- 2.2 +- 2.6) x 10^{-4}. The \bar B ->D^*K^{*-} branching ratios are the averages of those corresponding to the 00 and 11 helicity states. The errors shown are statistical and systematic, respectively.Comment: 9 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, Published in Phys.Rev.Lett.88:101803,200