Effect of fall characteristics on the severity of hip impact during a fall on the ground from standing height.

The magnitude of hip impact force during a fall on the ground (i.e., concrete surface) from standing height was determined. We found that this force decreases up to 59%, depending on how they land on the ground. INTRODUCTION: We determined the magnitude of hip impact force that humans may experience in the event of a fall from standing height on the ground, in order to examine how the hip impact force was affected by characteristics of a fall. METHODS: Twenty subjects mimicked a typical older adults' falls on a mat. Trials were acquired with three initial fall directions: forward, sideways, and backward. Trials were also acquired with three knee positions at the time of hip impact: knee together, knee on the mat, and free knee. During falls, attenuated vertical hip impact forces and corresponding depression of the mat were measured via a force plate placed under the mat and motion capture system, respectively. Using a mass-spring model, actual hip impact force and body stiffness during a fall on the ground were estimated. RESULTS: Hip impact force averaged 4.0 kN (SD = 1.7). The hip impact force was associated with knee condition (F = 25.6, p < 0.005), but not with fall direction (F = 0.4, p = 0.599). Compared with "knee on the mat," hip impact force averaged 59% and 45% greater in "free knee" and "knee together," respectively (4.6 versus 2.9 kN, p < 0.005; 4.3 versus 2.9 kN, p < 0.005). However, the hip impact force did not differ between "free knee" and "knee together (4.6 versus 4.3 kN, p = 0.554). CONCLUSION: Our results suggest that hip fracture risk during a fall decreases substantially, depending on how they land on the ground, informing the development of safe landing strategies to prevent fall-related hip fractures in older adults.

A phase Ib study of selumetinib (AZD6244, ARRY-142886) in combination with sorafenib in advanced hepatocellular carcinoma (HCC).

BACKGROUND: Treatment with sorafenib, although associated with inhibition of tumour growth and angiogenesis in in vivo studies, leads to up-regulation of pERK. The addition of MEK inhibition could potentially abrogate this effect and potentiate anti-tumour activity. This phase I study investigated the maximum tolerated dose (MTD), safety, tolerability, pharmacokinetics (PK) and biomarker correlates of selumetinib combined with sorafenib in patients with advanced hepatocellular carcinoma (HCC). METHODS: Patients with Child-Pugh (CP) score ≤7 were treated with 400 mg twice daily of sorafenib with escalating doses of selumetinib in a 3 + 3 study design. The dose-limiting toxicity (DLT) evaluation period was 28 days. PK of selumetinib was determined. Angiogenic effect was evaluated with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). RESULTS: Twenty-seven patients of Asian ethnicity were enrolled. The MTD was selumetinib 75 mg daily with sorafenib 400 mg twice daily. DLT included grade 3 transaminitis, diarrhoea and fatigue. Most common treatment-related adverse events at MTD (all grades) were diarrhoea (85%), rash (59%), hypertension (44%), fatigue (30%), anorexia (22%) and hand-foot syndrome (22%). Four patients (15%) had PR and 13 (48%) had SD. PR or SD was observed for ≥6 months in seven patients. The median overall survival was 14.4 months. Selumetinib exposures in combination with sorafenib were comparable to other monotherapy studies. A reduction in permeability-surface area product noted in DCE-MRI with treatment correlated with worse survival outcomes. CONCLUSION: The MTD of selumetinib was 75 mg daily when combined with sorafenib 400 mg twice a day in CP ≤7 HCC. Acceptable adverse events and encouraging anti-tumour activity warrant further evaluation. DCE-MRI findings deserve prospective evaluation. CLINICALTRIALSGOV IDENTIFIER: NCT01029418.

The proteins (12 and 15 kDa) isolated from heat-killed Lactobacillus plantarum L67 induces apoptosis in HT-29 cells.

A number of scientific studies have revealed that Lactobacillus strains have beneficial bioactivities in the gastrointestinal tract. In this study, the production of intracellular reactive oxygen species (ROS) and the amounts of intracellular calcium, protein kinase C activity, cytochrome c, Bid, Bcl-2, Bax and the apoptosis-mediated proteins [caspase-8, caspase-3 and poly ADP ribose polymerase (PARP)] were evaluated to understand the induction of programmed cell death in HT-29 cells by Lactobacillus plantarum L67. The results obtained from this study indicated that the relative intensities of the apoptotic-related factors (intracellular ROS and intracellular calcium) and of apoptotic signals (Bax and t-Bid) increased with increasing concentrations of the membrane proteins isolated from heat-killed L. plantarum L67, whereas the relative intensities of cytochrome c, Bcl-2, caspase-8, caspase-3 and PARP decreased. This study determines whether proteins (12 and 15 kDa) isolated from heat-killed L. plantarum L67 induce programmed cell death in HT-29 cells. Proteins isolated from L. plantarum L67 can stimulate the apoptotic signals and then consequently induce programmed cell death in HT-29 cells. The results in this study suggest that the proteins isolated from L. plantarum L67 could be used as an antitumoural agent in probiotics and as a component of supplements or health foods.

Bioactivity of proteins isolated from Lactobacillus plantarum L67 treated with Zanthoxylum piperitum DC glycoprotein.

Lactobacilli in the human gastrointestinal tract have beneficial effects on the health of their host. To enhance these effects, the bioactivity of lactobacilli can be fortified through exogenous dietary or pharmacological agents, such as glycoproteins. To elucidate the inductive effect of Zanthoxylum piperitum DC (ZPDC) glycoprotein on Lactobacillus plantarum L67, we evaluated the radical-scavenging activity, anti-oxidative enzymes (SOD, GPx and CAT), growth rate, ATPase activity and ß-galactosidase activity of this strain. When Lact. plantarum L67 was treated with ZPDC glycoprotein at different concentrations, the intensities of a few SDS-PAGE bands were slightly changed. The amount of a 23 kDa protein was increased upon treatment with increasing concentrations of ZPDC glycoprotein. The results of this study indicate that the radical-scavenging activity for O2(-) and OH¯, but not for the DPPH radical, increased in a concentration-dependent manner after treatment with ZPDC glycoprotein. The activation of anti-oxidative enzymes (SOD, GPx and CAT), growth rate and ß-galactosidase activity also increased in a concentration-dependent manner in response to ZPDC glycoprotein treatment, whereas ATPase activity was decreased. In summary, ZPDC glycoprotein stimulated an increase in the bioactivity of Lact. plantarum L67. Significance and impact of the study: This study demonstrated that Lactobacillus plantarum L67 possesses anti-oxidative activity. This strain of lactic bacteria has been known to have various probiotic uses, such as yogurt starters and dietary additional supplements. We found, through this experiment, that the protein has a strong anti-oxidative character, and the activity can be enhanced by treatment with Zanthoxylum piperitum DC (ZPDC) glycoprotein. This study may be application of Lact. plantarum L67 treated by ZPDC glycoprotein in yogurt fermentation. It could be one of the avenues of minimizing yogurt postacidification during storage. In addition, it can be manufactured and incorporated in food products without losing viability and functionality of Lact. plantarum L67.

Effects of hip muscle activation on the stiffness and energy absorption of the trochanteric soft tissue during impact in sideways falls.

The trochanteric soft tissue attenuates impact force or absorbs impact energy during a fall on the hip (thereby helps to reduce a risk of hip fracture). While the benefits should be affected by contractions of muscles spanning the hip joint, no information is available to date. We examined how the stiffness (force attenuation capacity) and energy absorption of the trochanteric soft tissue were affected by hip muscle activation during a fall. Thirteen healthy young individuals (5 males, 8 females) participated in the pelvis release experiment. Falling trials were acquired with three muscle contraction conditions: 0-20% ("relaxed"), 20-50% ("moderate"), and 60-100% ("maximal") of the maximal voluntary isometric contraction of the gluteus medius muscle. During trials, we measured real-time force and deformation behaviour of the trochanteric soft tissue. Outcome variables included the stiffness and energy absorption of the soft tissue. The stiffness and energy absorption ranged from 56.1 to 446.9 kN/m, and from 0.15 to 2.26 J, respectively. The stiffness value increased with muscle contraction, and 59% greater in "maximal" than "relaxed" condition (232.2 (SD = 121.4) versus 146.1 (SD = 49.9)). However, energy absorption decreased with muscle contraction, and 58.9% greater in "relaxed" than "maximal" condition (0.89 (SD = 0.63) versus 0.56 (SD = 0.41)). Our results provide insights on biomechanics of the trochanteric soft tissue ("natural" padding device) during impact stage of a fall, suggesting that soft tissues' protective benefits are largely affected by the level of muscle contraction.

The Houdini effect--an unusual case of blunt abdominal trauma resulting in perforative appendicitis.

We present a unique case of perforative appendicitis that occurred in an adult following blunt abdominal trauma. This case represents the first such reported case from Ireland. It also represents a modern practical example of Laplace's theory of the effect of increased pressure on colonic wall tension leading to localized perforation, and serves to highlight not only the importance in preoperative imaging for blunt abdominal trauma, but also the importance of considering appendiceal perforation.

Adenoma malignum of the uterine cervix: ultrasonographic findings in 11 patients.

OBJECTIVE: To evaluate the ultrasonographic features of adenoma malignum, a minimal deviation adenocarcinoma of the uterine cervix. METHODS: Eighteen consecutive patients with pathologically confirmed adenoma malignum were enrolled in this study at two institutions. Preoperative ultrasound examination was performed and the results were available in 11 patients. We analyzed retrospectively the gray-scale ultrasound findings for the following morphologic characteristics: cervical enlargement, as well as size, location and ultrasonographic characteristics of lesions. In five patients we also evaluated Doppler features with regard to intralesional vascularity. RESULTS: The cervix was enlarged in 73% (8/11) of cases. The mean greatest tumor diameter was 4.2 (range, 2.5-6.8) cm. In five (45%) cases, the cervix was completely infiltrated by the tumor. At gray-scale ultrasound examination, three (27%) tumors were multilocular lesions, four (36%) were multilocular lesions with solid components and four (36%) were solid lesions. In the multilocular lesions with or without a solid component, locules tended to be 1 cm or less in average diameter (86%, 6/7 cases) and there tended to be 11-20 in number (57%, 4/7 cases). In most (57%, 4/7) cases the locular fluid was homogeneously hypoechoic. Most (75%, 3/4) solid lesions manifested heterogeneous echogenicity. The five (100%) tumors examined with Doppler manifested moderate or abundant color content on color or power Doppler. CONCLUSIONS: Adenoma malignum can appear sonographically as solid, multilocular and multilocular solid cervical lesions. Awareness of its clinical and ultrasonographic features might improve diagnosis before surgery.

Differentiating blood samples from scrapie infected and non-infected hamsters by detecting disease-associated prion proteins using Multimer Detection System.

This communication describes the application of a modified sandwich enzyme-linked immunosorbent assay (ELISA), termed Multimer Detection System (MDS) for the detection of disease-associated multimeric forms of the prion protein (PrPd) in hamster blood. PrPd was detected in plasma of prion-affected hamsters while MDS revealed no PrPd in identically-treated plasma of healthy animals. This is the first report of a single ELISA- based immune detection of PrPd from blood samples.

Protein tyrosine phosphatase epsilon is a negative regulator of FcepsilonRI-mediated mast cell responses.

Modulation of mast-cell activation may provide novel ways to control allergic diseases. Here, we show that protein tyrosine phosphatase epsilon (PTPepsilon; Ptpre) plays key regulatory roles during mast-cell activation mediated by the high-affinity IgE receptor (FcepsilonRI). Bone marrow-derived mast cells (BMMC) from Ptpre(-/-) mice exhibited enhanced FcepsilonRI-induced Ca(2+) mobilization and mitogen-activated protein kinase (MAPK) (JNK and p38) activation, and showed corresponding enhancement of evoked degranulation and cytokine production, but not leukotriene production. Examination of proteins linking tyrosine kinase activation and Ca(2+) mobilization revealed that the absence of PTPepsilon leads to increased phosphorylation of the linker for activation of T cells and SH2 domain-containing leucocyte phosphoproteins of 76 kDa, but not Grb2-associated binder-2 (Gab2). Because Gab2 is considered to be situated downstream of Fyn kinase, we reasoned that Fyn may not be a target of PTPepsilon. In the event, Syk but not Lyn was hyperphosphorylated in PTPepsilon-deficient BMMC. Thus, PTPepsilon most likely exerts its effects at the level of Syk, inhibiting downstream events including phosphorylation of SLP-76 and linker of activated T cells and mobilization of Ca(2+). Consistent with the in vitro data, antigen- and IgE-mediated passive systemic anaphylactic reactions were augmented in Ptpre(-/-) mice. Given that the number of mast cells is unchanged in these mice, this observation most likely reflects alterations of mast cell-autonomous signalling events. These data suggest that PTPepsilon negatively regulates FcepsilonRI-mediated signalling pathways and thus constitutes a novel target for ameliorating allergic conditions.

Inhibitory effect of ZPDC glycoprotein on the expression of inflammation-related cytokines through p38 MAP kinase and JNK in lipopolysaccharide-stimulated RAW 264.7 cells.

OBJECTIVE: This study was carried out to investigate the anti-inflammatory potentials of 24 kDa glycoprotein isolated from Zanthoxylum piperitum DC fruit (ZPDC glycoprotein) in lipopolysaccharide (LPS)-stimulated murine macrophage cell line (RAW 264.7 cells). MATERIAL AND METHODS: RAW 264.7 cells were treated with ZPDC glycoprotein (50-200 microg/ml) in presence of LPS (2 microg/ml). The changes of the levels of inflammation-related factors were determined by using Western blot, EMSA, and RT-PCR. RESULTS: ZPDC glycoprotein has inhibitory effects on the phosphorylation of p38 mitogen-activated protein (MAP) kinase and c-Jun N-terminal kinase (JNK), on the DNA binding activity of activator protein-1 (AP-1), and on the expression of c-Jun and c-Fos in LPS-stimulated RAW 264.7 cells. Interestingly, the DNA binding activity of AP-1 was attenuated by treatment with inhibitors of p38 MAP kinase and JNK. In addition, ZPDC glycoprotein (200 microg/ml) not only diminished the production of superoxide anion, hydrogen peroxide, and nitric oxide, but also suppressed the expression of pro-inflammatory cytokines (IL-1 beta, IL-6, and TNF-alpha) and proteins (iNOS, COX-2, and MMP-9) in LPS- stimulated RAW 264.7 cells. CONCLUSIONS: The present study demonstrates that ZPDC glycoprotein is a natural anti-oxidant and one of the modulators of pro-inflammatory signal transduction pathways in RAW 264.7 cells.

Soft tissue stiffness over the hip increases with age and its implication in hip fracture risk in older adults.

Risk of hip fracture depends on the bone strength as well as the impact force delivered to the proximal femur during falls, and femoral soft tissue may help to reduce the hip fracture risk by attenuating the impact force. Femoral soft tissue stiffness was measured from a large sample, and compared how this was affected by age, gender and site. One hundred fifty healthy individuals (fifty-two young (aged between 19 and 29), forty-eight middle-aged (30-64), and fifty old (over 65)) participated. Each age group included an equal number of males and females. Using an automated hand-held indentation device, soft tissue stiffness was measured over twelve sites with respect to the greater trochanter (GT). For both left and right hips, the stiffness was associated with age (p < 0.0005), gender (p < 0.0005), and site (p < 0.0005). On average, the stiffness was 26% greater in older than young adults (321.5 versus 254.3 N/m). On average across twelve sites, the regression analysis indicated that the stiffness increases 1.33 N/m every year ("soft tissue stiffness over the hip = 1.33*age + 221.8"; R = 0.518, p < 0.0005). Furthermore, the stiffness was 18% greater in male than female (308.8 versus 262.6 N/m), and differed across twelve sites over the hip, being greatest (424.2 N/m) at the GT, and least (206.3 N/m) at the superior gluteal region. The results provide insights into the shock absorbing property of soft tissue over the hip, and inform the improvement of fall-related injury prevention interventions (i.e., hip protector, safe landing strategies) in older adults.

A review of neonatal attendances out of hours in a Dublin maternity hospital.

UNLABELLED: BACKGROUND All neonates have free open access to the Baby Clinic at the maternity hospitals in Dublin for assessment of neonatal health issues. Through observation, however there is an increase in number of neonates attending the hospital outside the Baby Clinic hours. AIMS: To determine the number of neonates attending the acute neonatal service out of hours and to identify the percentage of neonates treated as true emergency. METHODS: Retrospective chart review over a twelve-month period. RESULTS: Seven hundred and thirty-two neonates attended the hospital out of hours. The majority were diagnosed with gastrointestinal problems (228/31%), jaundice (101/13.7%), respiratory problems (82/11.1%) and skin disorders (79/10.7%). Only 106 (14.4%) attendances warranted admissions. CONCLUSIONS: A large number of neonatal attendances did not require acute assessment out of hours and were managed by reassurance and maternal education. A centralized phone-in-triage system was suggested to relieve the strain on the acute neonatal service.

Encephalitis and retarded growth of chicks caused by Sitiawan virus, a new isolate belonging to the genus Flavivirus.

A new virus named Sitiawan virus (SV) was isolated from sick broiler chicks in chicken embryos. The virus replicated well with cytopathogenic effect (CPE) in the chicken B-lymphocyte cell line LSCC-BK3. The virus was an enveloped RNA virus of approximately 41 nm in size with hemagglutinating activity (HA) to goose erythrocytes. It was cross-reactive with Japanese encephalitis virus (JEV), a member of flaviviruses by HA inhibition tests but not by cross-virus neutralization tests. The cDNA fragment of NS5 gene was amplified with primers corresponding to NS5 gene of flaviviruses. The nucleotide sequences were 92% homologous to Tembusu virus, a member of the mosquito-borne virus cluster of the genus Flavivirus. In cross-neutralization tests with Tembusu virus, antiserum to SV did not neutralize Tembusu virus, and antiserum to Tembusu virus neutralized more weakly to SV than against homologous virus. These results indicate that SV is a new virus which can be differentiated serologically from Tembusu virus but is otherwise similar with respect to nucleotide sequence. The virus causes encephalitis, growth retardation, and increased blood glucose levels in inoculated chicks.

Methylmercury-induced neurotoxicity in cerebral neuron culture is blocked by antioxidants and NMDA receptor antagonists.

The neurotoxic effects of methylmercury on cerebral neuron cultures derived from neonatal mouse were studied. Exposure of cerebral neurons to methylmercury chloride resulted in significant cell damage and death in a time-dependent manner in cerebral neuron cultures. The methylmercury neurotoxicity was blocked by oxygen radical scavengers such as glutathione, catalase, selenium, and cysteine. Antagonists of the N-methyl-D-aspartate (NMDA) receptor, including MK-801 (a non-competitive NMDA antagonist), D-2-amino-5-phosphonovaleric acid (APV) (a competitive NMDA antagonist), and 7-chlorokynurenic acid (an antagonist at the glycine site associated with the NMDA receptor), similarly blocked methylmercury-induced neurotoxicity in cerebral neuron cultures. These results indicate that both oxygen radicals and excitotixic amino acids are involved in the methylmercury-induced neurotoxicity of cerebral neuron cultures.

Spectroscopic and functional studies of a novel quadruple myoglobin variant with increased peroxidase activity.

A quadruple variant of horse heart myoglobin (Thr39Ile/Lys45Asp/Phe46Leu/Ile107Phe) that exhibits significantly (approximately 25-fold) greater peroxidase activity than the wild-type protein has been studied to determine its midpoint reduction potential (24(2) mV vs. SHE; pH 6.0, mu = 0.1 M, 25 degrees C) and to characterize the kinetics of its reaction with hydrogen peroxide. In addition, Fourier transform infrared (FTIR) spectra of the carbonyl and azide adducts of the protein have been obtained to gain initial insight into the effects of these substitutions on the ligand binding properties of the reduced and oxidized variant. All of the results obtained in this work are consistent with a variant heme binding pocket with increased hydrophilic character.

Glycoprotein isolated from Solanum nigrum L. inhibits the DNA-binding activities of NF-kappaB and AP-1, and increases the production of nitric oxide in TPA-stimulated MCF-7 cells.

Solanum nigrum L. (SNL) has been used in traditional folk medicine to treat numerous cancers. We isolated a glycoprotein (150 kDa) from SNL and tested its effect on the modulation of transcriptional factors (NF-kappa B and AP-1) and iNO production in TPA induced-MCF-7 cells, which are part of the human breast cancer cell line, without estrogen receptors. However, the mechanism of SNL glycoprotein in pharmacological and biochemical actions in cancer cells has not been studied. To test the effect of SNL glycoprotein on the DNA-binding activities of nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1), and nitric oxide (NO) production, these experiments were carried out using electrophoretic mobility shift assays (EMSA), western blot analysis, and the Griess method. Results in this experiment showed that SNL glycoprotein inhibits 12-O-Tetra decanoylphorbol-13-acetate (TPA; 100 nM)-induced DNA-binding activities of NF-kappaB and AP-1, and enhances NO production in MCF-7 cells. That is, our results indicated that SNL glycoprotein has the capacity to modulate the TPA-induced DNA-binding activities of transcription factors and NO production, which play a critical role with respect to cytotoxicity in MCF-7 cells. Therefore, SNL glycoprotein might be one of the agents that blocks TPA-mediated signal responses in tumor cells.

Antioxidant activity of a Rhus verniciflua Stokes ethanol extract.

A fractionated ethanol extract derived from Rhus Verniciflua Stokes (RVS) was assessed in both organic and aqueous media for the purpose of characterizing the mechanisms of antioxidant activity. RVS, an indigenous plant to Korea, was initially extracted with ethanol and characterized to contain a 90 KDa-ABTS reactive protein possessing 0.662 ng/mg copper. This characterization suggested that a primary component of RVS was Laccase, an oxidase enzyme complex. RVS exhibited a significant (P < 0.01) concentration-dependent inhibition of linoleic acid oxidation in an emulsion system up to 48 hours of incubation. Free radical scavenging activity of both a stable radical (e.g DPPH) and hydroxyl (e.g. *OH) radical followed a concentration-dependent pattern in different model systems. Using a liposome model with peroxyl radicals generated by AAPH, a significant extension of both the lag phase and a reduction of peak propagation of peroxyl radicals by RVS over a concentration range of 1 to 10 microg/ml was observed. RVS ethanol extract was also found to protect human low-density lipoprotein (LDL) from oxidative modification, mediated by cupric ion at 37 degrees C. Finally, RVS was found to be effective at protecting against plasmid DNA strand breakage induced by peroxyl free radicals in an aqueous medium. Our findings show that the ethanol fraction derived from RVS contained significant antioxidant activity in both polar and non-polar mediums.

Antitumorigenic and cytotoxic properties of an ethanol extract derived from Rhus verniciflua Stokes (RVS).

In this study, the antioxidant, cytotoxic, and antitumorigenic activities of a fractionated, ethanol extract derived from Rhus verniciflua Stokes (RVS), a plant indigenous to Korea, China, and Japan, were determined. Physicochemical analysis and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) results indicated that the active component of a Sephadex G-150-fractionated RVS extract (PII fraction) was a copper-containing glycoprotein, possibly a plant laccase. Antioxidant activity of the fractionated RVS extract, observed in both aqueous and lipid in vitro oxidation reactions using 1,1-diphenyl 2-picrylhydrazyl (DPPH) radical, site-specific Fenton-reaction deoxyribose, and a model lipid emulsion test system, indicated an affinity for protection against hydroxyl and peroxyl radicals. Cultured mouse brain neurons were protected against glucose oxidase-induced hydroxyl radical in the presence of the fractionated RVS extract (e.g., 58% protection at 4.9 microM and 95% protection with 22.7 microM RVS). RVS was further shown to protect against in vitro Fenton-reaction-induced single- and double-strand scission in supercoiled plasmid DNA. Further testing for bioactivity of the fractionated RVS extract was based on the affinity to inhibit cell proliferation in cultured HeLa and CT-26 tumor cells. The presence of RVS resulted in 70% cell death after 24 h of incubation in both cell lines at a minimum concentration of 2.48 microM RVS. Data demonstrate multiple bioactive chemopreventative properties of a Sephadex G-150-fractionated extract derived from RVS.

Rapid prenatal diagnosis of chromosome abnormalities.

The aim of the present work was to examine the efficacy of using FISH for the rapid prenatal diagnosis of common chromosome aneuploidies. A total of 100 analyses over a six month period were included in the study. Diagnosis was possible in all cases. A mosaic for trisomy 21 proved, by comparison with an extensive analysis of long term cultures, to be an apparent false positive. Otherwise the technique was reliable, accurate and relatively straightforward to perform. Results could be available within 24 hrs. In most cases an additional long term full analysis was also done, so as to exclude rarer aneuploidies and structural rearrangements. This methodology is seen as a useful addition to the prenatal diagnostic repertoire.