Unaltered Graft Survival and Intragraft Lymphocytes Infiltration in the Cardiac Allograft of Cxcr3−/- Mouse Recipients

Previous studies showed that absence of chemokine receptor Cxcr3 or its blockade prolong mouse cardiac allograft survival. We evaluated the effect of the CXCR3 receptor antagonist MRL-957 on cardiac allograft survival, and also examined the impact of anti-CXCR3 mAb in human CXCR3 knock-in mice. We found only a moderate increase in graft survival (10.5 and 16.6 days, p < 0.05) using either the antagonist or the antibody, respectively, compared to control (8.7 days). We re-evaluated cardiac allograft survival with two different lines of Cxcr3^−/- mice. Interestingly, in our hands, neither of the independently derived Cxcr3^−/- lines showed remarkable prolongation, with mean graft survival of 9.5 and 10.8 days, respectively. There was no difference in the number of infiltrating mononuclear cells, expansion of splenic T cells or IFN-γ production of alloreactive T cells. Mechanistically, an increased other chemokine receptor fraction in the graft infiltrating CD8 T cells in Cxcr3^−/- recipients compared to wild-type recipients suggested compensatory T-cell trafficking in the absence of Cxcr3. We conclude Cxcr3 may contribute to, but does not govern, leukocyte trafficking in this transplant model.     

Polygon interpolation for serial cross sections

In this paper, a new technique for contour interpolation between slices is presented. We assumed that contour interpolation is equivalent to the interpolation of a polygon that approximates the object shape. The location of each polygon vertex is characterized by a set of parameters. Polygon interpolation can be performed on these parameters. These interpolated parameters are then used to reconstruct the vertices of the new polygon. Finally, the contour is approximated from this polygon using a cubic spline interpolation. This new technique takes into account the shape, the translation, the size, and the orientation of the object's contours. A comparison with regular shape-based interpolation is made on several object contours. The preliminary results show that this new method yields a better contour and is computationally more efficient than shape-based interpolation. This technique can be applied to gray-level images too. The interpolation result of an MR image does not show artifact of intermediate substance commonly seen in a typical linear gray-level interpolation.     

Preparedness for Influenza Pandemic in Hong Kong Nursing Units

BACKGROUND: To present preparedness planning for an influenza pandemic for two nursing subunits: nursing services in hospitals and schools of nursing in universities. DISCUSSION: The preparedness plan is modeled on a modified Haddon matrix, a logical approach to identify measures appropriate for the pre-event, event, and postevent phases of an influenza pandemic. For the pre-event phase, the objective is to ensure preparedness for the potential pandemic outbreak through training, communication, surveillance, infection control, and vaccination. Once the pandemic outbreak is declared, the aim is to implement effective measures to ensure a rapid and appropriate response. For the postevent phase, the plan is focused on the restoration of core functions, vigilance for a second or possibly more waves of the pandemic, and psychosocial support to staff and students. CONCLUSION: Measures required to prepare for, respond to, and manage the consequences of influenza pandemic are identified. This planning indicates the need to balance a logical approach with contextual perspectives and the importance for nursing leaders to develop plans for subunits of larger entities.     

The relationship between hypertension and anxiety or depression in Hong Kong Chinese

BACKGROUND:

Psychosocial stress can be the cause or the consequence of hypertension.

OBJECTIVE:

To study the association between hypertension and anxiety or depression in adults from Hong Kong, China.

SUBJECTS AND METHODS:

Patients with diagnosed hypertension (n=197) were recruited to complete the Hospital Anxiety and Depression Scale (HADS) questionnaire. The control group comprised 182 normotensive subjects recruited using random telephone numbers.

RESULTS:

The score in the anxiety subscale (HADS-A) of the HADS correlated with age (r= −0.23, P<0.001) and sex (r=0.11, P=0.042), and was found to be higher in women. The score in the depression subscale (HADS-D) correlated with age (r=0.17, P=0.003) and hypertension (r=0.12, P=0.039), but not with sex (r=0.02, P=0.68). When the control subjects were matched for sex and age with the subjects with hypertension, the mean HADS-A score was 5.51±0.41 in 113 hypertensive subjects and 4.38±0.39 in 113 normotensive subjects (P=0.047). The mean HADS-D score was 5.56±0.39 in the hypertensive and 4.76±0.32 in the normotensive subjects (P=0.11). Multiple regression analysis using data from both groups indicated that the HADS-A score was related to the HADS-D score (β=0.49, P<0.001), age (β= −0.25, P<0.001) and sex (β=0.12, P=0.01) (R²=0.28), whereas the HADS-D score was related to the HADS-A score (β=0.48, P<0.001), age (β=0.30, P<0.001), positive smoking status (β=0.13, P=0.004) and lack of exercise habit (β=0.12, P=0.008) (R²=0.31). Hypertension was related to waist circumference, history of parental hypertension and age (R²=0.38, P<0.001). Anxiety and depression scores were rejected as independent variables.

CONCLUSIONS:

Hypertension was associated with anxiety but not depression; however, age, history of parental hypertension and central obesity appeared to have a stronger association with hypertension in adults from Hong Kong.     

Optimal management of hypothyroidism,hypothyroxinaemia and euthyroid TPO antibody positivity preconception and in pregnancy

Normal physiological changes of pregnancy warrant the need to employ gestation specific reference ranges for the interpretation of thyroid function tests. Thyroid hormones play crucial roles in foetal growth and neurodevelopment which are dependent on adequate supply of maternal thyroid hormones from early gestation onwards. The prevention of significant adverse obstetric and neurodevelopmental outcomes from hypothyroidism requires a strategy of empirical levothyroxine dose increases and predictive dose adjustments in pregnancy combined with regular thyroid function testing, starting before pregnancy and until the postpartum period. Subclinical hypothyroidism has been associated with an increased risk of pregnancy loss and neurocognitive deficits in children, especially when diagnosed before or during early pregnancy. Whilst trials of levothyroxine replacement for mild hypothyroidism in pregnancy have not indicated definite evidence of improvements in these outcomes, professional guidelines recommend treatment, especially if evidence of underlying thyroid autoimmunity is present. Studies of isolated hypothyroxinaemia in pregnancy have shown conflicting evidence with regards to adverse obstetric and neurodevelopmental outcomes and no causative relationships have been determined. Treatment of this condition in pregnancy may be considered in those with underlying thyroid autoimmunity. Whilst the evidence for a link between the presence of anti‐TPO antibodies and increased risks of pregnancy loss and infertility is compelling, the results of ongoing randomized trials of levothyroxine in euthyroid women with underlying autoimmunity are currently awaited. Further studies to define the selection of women who require levothyroxine replacement and to determine the benefits of a predictive dose adjustment strategy are required.     

AT2R deficiency mediated podocyte loss via activation of ectopic hedgehog interacting protein (Hhip) gene expression

Angiotensin II type 2 receptor (AT₂R) deficiency in AT₂R knockout (KO) mice has been linked to congenital abnormalities of the kidney and urinary tract; however, the mechanisms by which this occurs are poorly understood. In this study, we examined whether AT₂R deficiency impaired glomerulogenesis and mediated podocyte loss/dysfunction in vivo and in vitro. Nephrin‐cyan fluorescent protein (CFP)‐transgenic (Tg) and Nephrin/AT₂RKO mice were used to assess glomerulogenesis, while wild‐type and AT₂RKO mice were used to evaluate maturation of podocyte morphology/function. Immortalized mouse podocytes (mPODs) were employed for in vitro studies. AT₂R deficiency resulted in diminished glomerulogenesis in E15 embryos, but had no impact on actual nephron number in neonates. Pups lacking AT₂R displayed features of renal dysplasia with lower glomerular tuft volume and podocyte numbers. In vivo and in vitro studies demonstrated that loss of AT₂R was associated with elevated NADPH oxidase 4 levels, which in turn stimulated ectopic hedgehog interacting protein (Hhip) gene expression in podocytes. Consequently, ectopic Hhip expression activation either triggers caspase‐3 and p53‐related apoptotic processes resulting in podocyte loss, or activates TGFβ1–Smad2/3 cascades and α‐SMA expression to transform differentiated podocytes to undifferentiated podocyte‐derived fibrotic cells. We analyzed HHIP expression in the kidney disease database (Nephroseq) and then validated this using HHIP immunohistochemistry staining of human kidney biopsies (controls versus focal segmental glomerulosclerosis). In conclusion, loss of AT₂R is associated with podocyte loss/dysfunction and is mediated, at least in part, via augmented ectopic Hhip expression in podocytes. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Estimation of the risk of bloodborne pathogens to health care workers after a needlestick injury in Taiwan

OBJECTIVES: To estimate the number of health care workers (HCWs) in Taiwan at risk annually for contracting hepatitis B virus (HBV), hepatitis C virus (HCV), and HIV after a needlestick and sharps injury (NSI) with a used hollow-bore needle. METHODS: All patients hospitalized in 1 tertiary hospital between September 1997 and June 1998 had routine pathological work-ups. On the first day of the months of September 1997, December 1997, March 1998, and June 1998, 1805 samples of deidentified residual sera randomly sampled from 18,474 inpatients older than 6 years were serologically tested for antigens to HBV (HBsAg and HBeAg) and antibodies to HCV (anti-HCV) and HIV (anti-HIV) with enzyme-linked immunosorbent assay reagents. The frequency of NSIs with contaminated devices in HCWs from 16 public teaching hospitals between July 1996 and June 1997 and the serologic results were used to extrapolate the estimated annual rate of seroconversion in HCWs after an NSI. RESULTS: Of the 1805 samples tested, 16.7% were seropositive for HBsAg (of which 1.7% were positive for HBeAg), 12.7% were positive for anti-HCV, and 0.8% were positive for anti-HIV. Of the 7550 NSIs reported by 8645 HCWs, 66.7% involved a contaminated hollow-bore needle. From these data, 308 to 924 HCWs were estimated to be at risk for contracting HBV; 334 to 836 were at risk for contracting HCV; and, at the most, 2 were at risk for contracting HIV. The estimated annual number of contaminated NSIs sustained by 4 categories of HCWs ranged from 0.3 to 0.7, resulting in 543 nurses, 113 technicians, 80 physicians, and 66 supporting staff to be at risk annually of acquiring HBV infection. The numbers of HCWs estimated to be at risk of acquiring HCV were 596 nurses, 90 physicians, 84 technicians, and 30 supporting staff. The risk of acquiring HIV was low, with 1 nurse and possibly 1 other staff potentially exposed annually. CONCLUSIONS: Our estimates of the risk for seroconversion after an NSI have demonstrated that an occult risk can be formulated into a quantifiable risk. The number of susceptible HCWs at risk for seroconversion is as many as 1762 annually. With the number of nurses employed and the frequency with which they use sharps and sustain an NSI, 64.7% of all possible seroconversions will be in the nursing staff. This is a salient reminder of the importance of the introduction of early training in safe-needle-handling techniques before nurses enter their internship in countries where safety equipment, safety instructions, and staff vaccination programs are absent.     

Establishment of a human acute promyelocytic leukemia-ascites model in SCID mice

Acute promyelocytic leukemia (APL) is an interesting model for cancer research because of the presence of the specific PML-RARalpha fusion gene associated with the clinical response to retinoic acid differentiation therapy. To better understand and improve differentiation induction with retinoic acid, we have established a human APL-ascites model in SCID mice using the NB4 human APL cell line. NB4 (1 x 10(6) cells) were transplanted into the peritoneum (IP) of SCID mice for 1 month. NB4 ascites cells (A-NB4) appeared, which were then engrafted in SCID mice periodically for 18 passages at an interval of 3 to 4 weeks with a 100% success rate of tumor induction. The mean survival times of SCID mice transplanted with 1 x 10(6) A-NB4 cells was 21.6 +/- 2.3 days. Analysis of the biologic characteristics of ninth passage NB4 ascitic cells was performed and they were found to have the morphologic, immunologic, cytogenetic, and molecular features of cultured NB4 cells. Furthermore, A-NB4 cells were capable of differentiating when treated with all-trans retinoic acid (ATRA), as manifested by enhanced NBT reduction and CD11b expression. In vivo treatment with ATRA in SCID mice for 4 days also increased NBT reduction by A-NB4 cells. ATRA treatment significantly prolonged survival time in the group after transplantation (28.1 +/- 6.8 to 29.1 +/- 8.4 days) compared with the control (P < .001). Furthermore, treatment with adriamycin, an effective chemotherapeutic drug in APL, had a strong growth suppressive effect on A-NB4 cells. These results demonstrate that this SCID-APL (NB4 ascites cells) model is a useful preclinical system for evaluating new or known drugs in the treatment of APL.