Analysis of procedure-related costs and proposed benefits of using patient-specific approach in total knee arthroplasty

Recently, patient-specific approaches to total knee arthroplasty (TKA) have been introduced that utilize preoperative magnetic resonance imaging data to manufacture custom cutting jigs specific to a patient's bony anatomy. These approaches intend to provide the benefits of accurate implant alignment while overcoming some of the proposed disadvantages of current computer navigation systems. In this study, a cost and benefit assessment of implementing the patient-specific approach compared to conventional and computer-navigated TKA was conducted at a large academic medical center. Fixed and time-dependent operating room (OR) costs were determined and compared, as well as the cost for processing operative equipment and additional procedure-related expenditures. Overall, patient-specific TKA was not cost saving in this model on a per-case basis compared to conventional methods, although it was less costly overall to the institution compared to implementing intraoperative navigation. However, the patient-specific approach provides the institution with an additional 28 minutes of available OR time per intervention based on reduction in preparation and operative times compared to conventional methods and an additional 67 minutes compared to computer navigation based on this model. This time savings is likely to provide a greater economic impact to the health care system than implant-related cost savings.     

Chronic exposure to sub-lethal concentration of a glyphosate-based herbicide alters hormone profiles and affects reproduction of female Jundiá (Rhamdia quelen)

This work was carried out to verify the effect of a glyphosate-based herbicide on Jundiá hormones (cortisol, 17β-estradiol and testosterone), oocyte and swim-up fry production. Earthen ponds containing Jundiá females were contaminated with glyphosate (3.6 mg/L); blood samples were collected from eight females from each treatment immediately before, or at 1, 10, 20, 30 and 40 days following contamination. A typical post-stress rise in cortisol levels was observed at the 20th and 40th days following exposure to glyphosate. At the 40th day, 17β-estradiol was decreased in the exposed females. A similar number of oocytes were stripped out from females from both groups; however, a lower number of viable swim-up fry were obtained from the herbicide exposed females, which also had a higher liver-somatic index (LSI). The results indicate that the presence of glyphosate in water was deleterious to Rhamdia quelen reproduction, altering steroid profiles and egg viability.     

Excessive daytime sleepiness and hepatic encephalopathy: it is worth asking

The relationship between hepatic encephalopathy (HE) and the sleep-wake disturbances exhibited by patients with cirrhosis remains debated. The aim of this study was to examine the usefulness of sleep-wake interview within the context of HE assessment. One-hundred-and-six cirrhotic patients were asked three yes/no questions investigating the presence of difficulty falling asleep, night awakenings and daytime sleepiness. All underwent formal HE assessment, quantitative electroencephalography and standardised psychometry. Fifty-eight were monitored for 8?±?6 months in relation to the occurrence of HE. Patients complaining of daytime sleepiness (n?=?75, 71 %) had slower EEGs than those who did not report it (relative alpha power: 37?±?19 vs. 48?±?17 %, p?<?0.05). In addition, daytime sleepiness was associated with the presence of portal-systemic shunt (79 vs. 57 %, p?<?0.05) and HE history (72 vs. 45 %, p?<?0.05). Finally, the absence of excessive daytime sleepiness had a Negative Predictive Value of 92 % (64–100) in relation to the development of HE during the follow-up period. These data support the appropriateness of adding a yes/no question on the presence of excessive daytime sleepiness to routine assessment of patients with cirrhosis, to help identify those who do not need further, formal HE screening.     

Structure-based approach to rationally design a chimeric protein for an effective vaccine against Group B Streptococcus infections

Structural vaccinology is an emerging strategy for the rational design of vaccine candidates. We successfully applied structural vaccinology to design a fully synthetic protein with multivalent protection activity. In Group B Streptococcus, cell-surface pili have aroused great interest because of their direct roles in virulence and importance as protective antigens. The backbone subunit of type 2a pilus (BP-2a) is present in six immunogenically different but structurally similar variants. We determined the 3D structure of one of the variants, and experimentally demonstrated that protective antibodies specifically recognize one of the four domains that comprise the protein. We therefore constructed a synthetic protein constituted by the protective domain of each one of the six variants and showed that the chimeric protein protects mice against the challenge with all of the type 2a pilus-carrying strains. This work demonstrates the power of structural vaccinology and will facilitate the development of an optimized, broadly protective pilus-based vaccine against Group B Streptococcus by combining the uniquely generated chimeric protein with protective pilin subunits from two other previously identified pilus types. In addition, this work describes a template procedure that can be followed to develop vaccines against other bacterial pathogens.     

Properties of mouse leukemia viruses XVIII. Effective treatment of AKR leukemia with antibody to gp7l eliminates the neonatal burst of ecotropic AKR virus producing cells

To suppress spontaneous leukemia, treatment of AKR mice with antibody to the murine leukemia virus (MuLV) major glycoprotein (gp71) must commence during a narrow “window” period between birth and Day 3. To examine the effect of treatment on virus expression, infectious MuLV cell centers (ICCs), free MuLV, and viral antigen presence were examined in various organs of control and antibody-treated neonatal AKR mice. Ecotropic MuLV ICCs and viral antigens were found to increase 100-fold between Days 3 and 8 in thymuses, spleens, and livers in untreated mice. Quantitatively, spleens and livers had about 100-fold more viral ICCs than the thymus. After Day 8 viral ICCs persisted at plateau levels in all organs, with thymic ICCs 100-fold below spleens and livers. Maximal plateau levels of free ecotropic virus were reached only by Day 16. Xenotropic MuLV was occasionally isolated in ICC assays, but no recombinant MuLV was ever detected in any organ early in life. Viral p30 and gp7l antigen expression detected by immunofluorescent assays (IFA) closely corresponded to ICCs. In contrast, in AKR mice treated three or more times with gp7l antibody, MuLV ICCs were essentially undetectable during the first 3 weeks of life. In IFA, anti-gp7l-treated mice also had no virus antigen-positive cells in the organs tested. Spleen cells from control antibody-treated AKR mice were also treated in vitro with immune antibody and tested for virus- and antigen-positive cells. Anti-gp7l antibody did bind in vitro to virus-positive cells as measured by IFA but was neither cytotoxic nor reduced viral ICCs. However, the addition of complement to anti-gp7l antibody-coated cells resulted in a highly specific, effective killing of those cells scoring as viral ICCs. To determine the role of induction and/or clonal expansion of virus-positive cells relative to virus spread, perinatal F₁ (NIH × AKR) (by convention, maternal parent listed first in F₁ designations) and (BALB/c × AKR) mouse cells were assayed for ecotropic ICCs. Fv-1ⁿ permissive (NIH × AKR) mice had only slightly fewer ICCs, and the timing and distribution of virus release was similar to AKR mice. Fv-1^nb restrictive (BALB/c × AKR) mice had different kinetics of ICC formation. At plateau, the ICCs were severalfold lower than that in Fv-1ⁿ permissive mice, suggesting that an increase of virus-positive cells occurs during the neonatal period by means other than virus spread. However, virus spread may account for up to a 10-fold-increase in ICCs in AKR mice. The above data graphically demonstrated that the treatment “window” corresponded to a time just prior to the burst of ecotropic virus ICCs. The nature of ecotropic virus-positive cells and their elimination with treatment are discussed relative to later events in AKR leukemogenesis.     

Properties of mouse leukemia viruses XIII. Serum therapy of virus-induced murine leukemias

Treatment of STU mice with antiserum to the major glycoprotein (gp71) of Friend leukemia virus (FLV) was therapeutically active against massive infection with Friend or Rauscher viruses, whereas similar treatment with antisera to p12 and p15, two other proteins of the virion which are involved in surface reactions, were not effective. A more thorough study showed that the active principle is contained in the IgG fraction of gp71 antiserum and that treatment with this can lead to complete recovery of the mouse from FLV infection. As a consequence of the treatment, the host produces type-specific antibodies which are detectable by neutralization, radioimmunoassay with FLV gp71, and cytotoxic tests on FLV-infected cells. No significant change was observed in the pattern of autogenous antibodies directed against an AKR-type gp71 already present in normal mice. Treatment with immune serum instead of immune IgG or treatment with immune IgG at a later stage of infection with FLV (after 7 days p.i.) did not result in complete recovery of the mice. Paralysis of the host immune system by serum proteins and Friend virus, respectively, seems to be responsible for these phenomena. Some indication was obtained that the viral-induced paralysis can be overcome by combined inoculation of heterologous immune IgG and normal isogenic spleen and bone marrow cells.