Hybrid reflection retrieval method for terahertz dielectric imaging of human bone

Terahertz imaging is becoming a biological imaging modality in its own right, alongside the more mature infrared and X-ray techniques. Nevertheless, extraction of hyperspectral, biometric information of samples is limited by experimental challenges. Terahertz time domain spectroscopy reflection measurements demand highly precise alignment and suffer from limitations of the sample thickness. In this work, a novel hybrid Kramers-Kronig and Fabry-Pérot based algorithm has been developed to overcome these challenges. While its application is demonstrated through dielectric retrieval of glass-backed human bone slices for prospective characterisation of metastatic defects or osteoporosis, the generality of the algorithm offers itself to wider application towards biological materials.     

Caloxins: a novel class of selective plasma membrane Ca2+ pump inhibitors obtained using biotechnology

Plasma membrane Ca²⁺ pumps (PMCA) extrude cellular Ca²⁺ with a high affinity and hence play a major role in Ca²⁺ homeostasis and signaling. Caloxins (selective extracellular PMCA inhibitors) would aid in elucidating the physiology of PMCA. PMCA proteins have five extracellular domains (exdoms). Our hypotheses are: 1) peptides that bind selectively to each exdom can be invented by screening a random peptide library, and 2) a peptide can modulate PMCA activity by binding to one of the exdoms. The first caloxin 2a1, selected for binding exdom 2 was selective for PMCA (Ki = 529 μM). It has been used to examine the physiological role of PMCA. PMCA isoforms are encoded by four genes. PMCA isoform expression differs in various cell types, with PMCA1 and 4 being the most widely distributed. There are differences between PMCA1-4 exdom 1 sequences, which may be exploited for inventing isoform selective caloxins. Using exdom 1 of PMCA4 as a target, modified screening procedures and mutagenesis led to the high-affinity caloxin 1c2 (Ki = 2.3 μM for PMCA4). It is selective for PMCA4 over PMCA1, 2, or 3. We hope that caloxins can be used to discern the roles of individual PMCA isoforms in Ca²⁺ homeostasis and signaling. Caloxins may also become clinically useful in cardiovascular diseases, neurological disorders, retinopathy, cancer, and contraception.     

Measurement of c-myc oncogene expression provides an accurate prognostic marker for acral lentiginous melanoma.

Acral lentiginous melanoma is a particularly aggressive tumour with a worse prognosis than other varieties of primary cutaneous melanoma. In order to study the biology of this disease, the activity of the c-myc oncogene was studied in tumours from 45 patients using flow cytometry. High levels of oncoprotein were found in all tumours and exceeded that documented in other varieties of cutaneous melanoma. Survival analysis with stratification of patients according to oncogene activity provided a useful prognostic marker with shorter disease free interval (Log-Rank test, chi 2 = 16.7, P < 0.0001) and overall survival (Log-Rank test, chi 2 = 8.9, P = 0.002) in tumours with high oncoprotein levels. Multivariate analysis revealed c-myc oncogene expression to be more accurate in predicting clinical outcome than all existing clinicopathological parameters including the Breslow depth (Cox's proportional hazards model, P = 0.0011). This study provides biological evidence to explain the aggressive behaviour of acral melanoma and supports the application of oncogene measurement as an accurate prognostic marker.     

Norepinephrine and nomega-monomethyl-L-arginine in porcine septic shock: effects on hepatic O2 exchange and energy balance.

We compared the effects of norepinephrine (NOR; n = 11) and the nonselective nitric oxide synthase inhibitor Nomega-monomethyl-L-arginine (L-NMMA; n = 11) on hepatic blood flow (Q liv), O2 exchange, and energy metabolism over 24 h of hyperdynamic, normotensive porcine endotoxic shock. Endotoxin (ETX; n = 8) caused a continuous fall in mean arterial pressure (MAP) despite a sustained 50% increase in cardiac output (Q) achieved by adequate fluid resuscitation. NOR maintained MAP at preshock levels owing to a further rise in Q, while the comparable hemodynamic stabilization during L-NMMA infusion resulted from systemic vasoconstriction, increasing the systemic vascular resistance (SVR) about 30% from shock level after 6 h of treatment concomitant with a reduction in Q to preshock values. Whereas NOR also increased Q liv and, hence, hepatic O2 delivery (hDO2), but did not affect hepatic O2 uptake (hVO2), L-NMMA influenced neither Q liv nor hDO2 and hVO2. Mean capillary hemoglobin O2 saturation (HbScO2) on the liver surface as well as HbScO2 frequency distributions, which mirror microcirculatory O2 availability, remained unchanged as well. Neither treatment influenced the ETX-induced derangements of cellular energy metabolism reflected by the progressive decrease in hepatic lactate uptake rate and increased hepatic venous lactate/pyruvate ratios. ETX nearly doubled the endogenous glucose production (EGP) rate, which was further increased with NOR, whereas L-NMMA nearly restored EGP to preshock levels. Nevertheless, despite the different mechanisms in maintaining blood pressure neither treatment influenced ETX-induced liver dysfunction.     

Screening for ovarian cancer using serum CA125 and vaginal examination: report on 2550 females

This study was undertaken to assess the effectiveness of using serum CA125 and vaginal examination as a screening test for ovarian cancer in apparently healthy females. Two thousand five hundred and fifty healthy females aged 40 and over were recruited to participate in a screening study involving a questionnaire, serum CA125 measurement and vaginal examination. Females with either an elevated CA125 level or abnormal vaginal examination had a pelvic ultrasound performed as a secondary procedure. The positive predictive values of an elevated serum CA125 level, and a combination of CA125 level measurement and vaginal examination for ovarian cancer, were 1/100 and 1/3, respectively. The specificities of serum CA125 levels, vaginal examination and both in combination were 96.1%, 98.5% and 99.9%, respectively. In postmenopausal females the positive predictive values were improved with CA125 measurement alone, giving a positive predictive value of 1/24. Seventeen females underwent operative procedure as a result of the screening—only one of these was for an ovarian cancer. The combination of serum CA125 measurement and vaginal examination is not an effective screening test in the general population, although in postmenopausal females it does achieve acceptable specificities and positive predictive values.     

Epstein–Barr virus mucocutaneous ulcer followed by Hodgkin lymphoma in multiple myeloma patient

Epstein–Barr virus mucocutaneous ulcers (EBV MCU) are B‐cell lymphoproliferative disorders associated with immunosuppression. We report EBV MCU in a multiple myeloma patient on lenalidomide maintenance after stem cell transplant that resolved with decreased immunosuppression. Furthermore, the subsequent development of classical Hodgkin lymphoma suggests an underlying predisposition to EBV‐driven lymphoproliferative disorders.     

Cue-based feeding for preterm infants: a prospective trial

We set out to test whether premature infants were able to be fed orally on feeding cues and be discharged home earlier than infants fed by traditional feeding regimens. Attainment of adequate growth, adverse events, and nursing time to provide care were also assessed. After screening, the recruited premature infants (< 36 wks post-conceptual age [PCA]) were divided into two feeding regimens. A control group of 40 infants was fed using an initial combination of scheduled gavage and bottle feeding and then graduating to demand feeds. The intervention group comprised 39 neonates who had gavage feeds discontinued at study entrance and fed orally on cues. Outcomes measured were: weight gain in grams/kg/day, length of stay (in days) after enrollment, PCA on entrance and at discharge, adverse events during feeding, number of cues per feed in the intervention group, and resource utilization using nurse/patient ratios. Differences between groups were evaluated using Mann-Whitney U test, Fisher's exact test, and regression analysis. Two-tailed P values of < 0.05 were considered significant. There was no difference between groups in the mean weight gain; in the control group mean weight gain was 12.5 gm/kg/day and in the intervention group 12.1 gm/kg/day ( P = 0.83). The average length of stay in the control group of 14.5 days was significantly longer than the 10.0 days in the intervention group ( P = 0.009). This difference remained significant after adjusting for gestational age at birth in regression analysis. The average total number of adverse events in the control group (12.5 events) was significantly greater than in the intervention group (3.5 events; P = 0.007). The mean PCA on study entry was 34.4 wks in both groups and on exit 36.5 wks in the control group and 35.8 wks in the intervention group, a significant difference ( P = 0.02), The intervention group elicited 2.8 cues/feed. The nurse to patient ratios was equal in both groups throughout the study period. Cue-based feeding was possible for premature infants with similar weight gain as traditional feeding without affecting workload. Hospitalization and adverse events were decreased.