Genomic description of acquired fluconazole- and echinocandin-resistance in patients with serial Candida glabrata isolates.

Candida glabrata is one of the most common causes of systemic candidiasis, often resistant to antifungal medications. To describe the genomic context of emerging resistance, we conducted a retrospective analysis of 82 serially collected isolates from 33 patients from population-based candidemia surveillance in the United States. We used whole-genome sequencing to determine the genetic relationships between isolates obtained from the same patient. Phylogenetic analysis demonstrated that isolates from 29 patients were clustered by patient. The median SNPs between isolates from the same patient was 30 (range: 7-96 SNPs), while unrelated strains infected four patients. Twenty-one isolates were resistant to echinocandins, and 24 were resistant to fluconazole. All echinocandin-resistant isolates carried a mutation either in the FKS1 or FKS2 HS1 region. Of the 24 fluconazole-resistant isolates, 17 (71%) had non-synonymous polymorphisms in the PDR1 gene, which were absent in susceptible isolates. In 11 patients, a genetically related resistant isolate was collected after recovering susceptible isolates, indicating in vivo acquisition of resistance. These findings allowed us to estimate the intra-host diversity of C. glabrata and propose an upper boundary of 96 SNPs for defining genetically related isolates, which can be used to assess donor-to-host transmission, nosocomial transmission, or acquired resistance. IMPORTANCE In our study, mutations associated to azole resistance and echinocandin resistance were detected in Candida glabrata isolates using a whole-genome sequence. C. glabrata is the second most common cause of candidemia in the United States, which rapidly acquires resistance to antifungals, in vitro and in vivo.

A computational framework for finding parameter sets associated with chaotic dynamics.

Many biological ecosystems exhibit chaotic behavior, demonstrated either analytically using parameter choices in an associated dynamical systems model or empirically through analysis of experimental data. In this paper, we use existing software tools (COPASI, R) to explore dynamical systems and uncover regions with positive Lyapunov exponents where thus chaos exists. We evaluate the ability of the software's optimization algorithms to find these positive values with several dynamical systems used to model biological populations. The algorithms have been able to identify parameter sets which lead to positive Lyapunov exponents, even when those exponents lie in regions with small support. For one of the examined systems, we observed that positive Lyapunov exponents were not uncovered when executing a search over the parameter space with small spacings between values of the independent variables.

Canine parasitic zoonoses in India: status and issues.

Dogs play valuable roles in human society. In addition to serving as pets and companions, dogs have also been important in hunting and, in recent times, as therapy animals. In India, the number of pet dogs is estimated to be around 5 million. The stray dog population in India is estimated to be 19 million and still increasing, due to ineffective control measures. Stray dogs pose substantial risks to public health due to injury and transmission of zoonoses such as rabies. Both pet and stray dogs may act as reservoirs of zoonotic parasites in India, which has a climate conducive to the environmental survival and transmission of many zoonotic parasites. At present, visceral larva migrans, cutaneous larva migrans and echinococcosis are the most important parasitic zoonoses in India. Leishmaniosis, dirofilariosis, Brugia malayi infection and giardiosis are potentially significant emerging parasitic zoonoses, and theleziosis, gnathostomiosis and dipylidiosis occur sporadically. Because of their biomedical and public health significance, and the lack of literature and compiled data on parasitic zoonoses of dogs in India, the authors provide a concise review on this topic along with potential control strategies.

Les chiens jouent un rôle précieux dans les sociétés humaines. En plus de servir d'animaux de compagnie, les chiens ont, depuis toujours, une fonction importante dans la chasse ainsi que, depuis peu, dans les thérapies assistées par l'animal. En Inde, on estime à environ 5 millions le nombre de chiens de compagnie. La population de chiens errants est estimée pour sa part à 19 millions d'individus et ne cesse de croître en raison de l'inefficacité des mesures de contrôle appliquées. Les chiens errants font peser des risques considérables sur la santé publique en raison des blessures qu'ils provoquent et de leur capacité à transmettre des zoonoses comme la rage. En outre, les chiens tant domestiques qu'errants sont des réservoirs potentiels pour nombre de parasites zoonotiques en Inde, pays dont le climat est propice à la survie de ces parasites dans l'environnement et à leur transmission. À l'heure actuelle, les zoonoses parasitaires les plus importantes en Inde sont le syndrome de larva migrans viscéral, le syndrome de larva migrans cutané et l'échinococcose. La leishmaniose, la dirofilariose, l'infection à Brugia malayi et la giardiose sont des zoonoses parasitaires émergentes potentiellement significatives tandis que la thélaziose, la gnathostomose et la dipylidiose font des incursions sporadiques. Compte tenu de l'importance biomédicale des maladies parasitaires zoonotiques du chien et de leur impact sur la santé publique en Inde, mais aussi du manque de publications scientifiques ou de données collectées les concernant, les auteurs font rapidement le point sur le sujet et proposent quelques stratégies de lutte possibles.

El perro cumple importantes funciones en la sociedad humana. Además de ser animal de compañía, también ha sido históricamente importante para la caza y, en los últimos tiempos, como animal terapéutico. Se calcula que en la India hay alrededor de 5 millones de perros que viven como mascota. Pero el país también alberga hoy, según los cálculos, una población de 19 millones de perros vagabundos, número que sigue creciendo debido a la ineficacia de las medidas de control. Estos perros suponen un importante riesgo para la salud pública, pues causan heridas y transmiten zoonosis como la rabia. El perro, ya sea mascota o vagabundo, puede ejercer de reservorio de parásitos zoonóticos en la India, cuyo clima favorece la supervivencia en el medio y la transmisión de muchos de tales parásitos. A día de hoy, las zoonosis parasitarias más importantes en el país son las de la larva migrante visceral, la larva migrante cutánea y la equinococosis. La leishmaniosis, la dirofilariosis, la infección por Brugia malayi y la giardiosis son zoonosis parasitarias emergentes que pueden llegar a cobrar importancia, mientras que la telaziosis, la gnatostomiosis y la dipilidiosis se dan esporádicamente. Los autores, dada la importancia que revisten las zoonosis parasitarias caninas desde el punto de vista biomédico y de salud pública, así como la falta de bibliografía y datos centralizados sobre su presencia en la India, hacen un breve repaso de la cuestión y apuntan a posibles estrategias de lucha.

Novel KDM6A (UTX) mutations and a clinical and molecular review of the X-linked Kabuki syndrome (KS2).

We describe seven patients with KDM6A (located on Xp11.3 and encodes UTX) mutations, a rare cause of Kabuki syndrome (KS2, MIM 300867) and report, for the first time, germ-line missense and splice-site mutations in the gene. We demonstrate that less than 5% cases of Kabuki syndrome are due to KDM6A mutations. Our work shows that similar to the commoner Type 1 Kabuki syndrome (KS1, MIM 147920) caused by KMT2D (previously called MLL2) mutations, KS2 patients are characterized by hypotonia and feeding difficulties during infancy and poor postnatal growth and short stature. Unlike KS1, developmental delay and learning disability are generally moderate-severe in boys but mild-moderate in girls with KS2. Some girls may have a normal developmental profile. Speech and cognition tend to be more severely affected than motor development. Increased susceptibility to infections, join laxity, heart, dental and ophthalmological anomalies are common. Hypoglycaemia is more common in KS2 than in KS1. Facial dysmorphism with KDM6A mutations is variable and diagnosis on facial gestalt alone may be difficult in some patients. Hypertrichosis, long halluces and large central incisors may be useful clues to an underlying KDM6A mutation in some patients.

Perfusionist techniques of reducing acute kidney injury following cardiopulmonary bypass: an evidence-based review.

Cardiac surgery utilizing cardiopulmonary bypass has come a long way since its introduction nearly 60 years ago. In the early days, end-organ damage was linked to contact of the blood with the extracorporeal circuit. One potential cardiac surgery complication known to result in significant morbidity and mortality is acute kidney injury (AKI). Causes of AKI are multifaceted, but most of them are associated with techniques that perfusionists employ during extracorporeal circuit management. These can cause patients to either go on dialysis or renal replacement therapy. Patients with AKI have longer lengths of stay and consume significant resources beyond those with normal kidney function. Few current evidence-based markers determine if the kidneys are adequately protected during surgery. Most relevant literature does not address perfusion-specific techniques that reduce the incidence of AKI. This paper reviews the pathophysiology of the kidney and focuses on perfusion techniques that may reduce the incidence of AKI.

Comparative review of One Health and Indigenous approaches to wildlife research in Inuit Nunangat.

There is increasing interest in One Health and Indigenous methodologies and approaches in wildlife research, but they are not widely used research applications in the Arctic. Both approaches are wide in scope and originate from different knowledge systems but are often compared synonymously. We review the literature of overlap between the term One Health and Inuit Qaujimajatuqangit (Inuit Indigenous Knowledge) throughout Inuit Nunaat on wildlife research. Three databases (SCOPUS, Web of Science, and BIOSIS) were used to find English language articles and books within the bounds of Inuit Nunaat. While One Health and Inuit Qaujimajatuqangit research approaches share synergies, they are fundamentally disparate owing to their differences in epistemology, including views on the natural environment and wildlife management. We describe current examples of One Health being operationalized in Inuit Nunaat and identify potential to address larger and more complex questions about wildlife health, with examples from terrestrial and marine Arctic wildlife. Both Indigenous methodologies and One Health naturally have a human component at their core, which seamlessly lends itself to discussions on wildlife management, as human actions and regulations directly impact environment and wildlife health.

Establishment of a European-type strain of Echinococcus multilocularis in Canadian wildlife.

In 2009, a haplotype closely related to European strains of Echinococcus multilocularis was detected in a dog from the Quesnel region of British Columbia, Canada. We now report the establishment of this same haplotype in 7 coyotes (Canis latrans) trapped within 40 km of Quesnel, BC. In addition, 3 coyotes and 1 red fox (Vulpes vulpes) harboured adult cestodes morphologically compatible with that of E. multilocularis (overall prevalence 33% in 33 carnivores). None of 156 potential intermediate hosts, including 131 representatives of two highly suitable rodent species, Peromyscus maniculatus and Microtus pennsylvanicus, trapped from a region 120-210 km south of Quesnel were infected. This report confirms the establishment and local transmission of a European-type strain of E. multilocularis (the causative agent of human alveolar hydatid disease), in wildlife in a forested region of North America where this cestode had not been previously detected, with significance for public and animal health.

Anorexia Nervosa in vivo cytokine production: a systematic review.

INTRODUCTION: The underlying psychobiology that contributes to Anorexia Nervosa (AN) onset and disease progression remains unclear. New research is emerging suggesting a possible link between inflammation and a variety of mental illnesses. Alterations of cytokines may play a role in the pathogenesis of AN. Some studies have found differences in the cytokine profile of those with AN compared to healthy controls, but results are heterogeneous. The aim of this work was to systematically review existing studies investigating in-vivo cytokine production in those with AN before and after weight restoration compared to controls. METHODS: A comprehensive literature search of four electronic databases (PubMed, PsychInfo, EMBASE and CINAH) was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines to identify human in-vivo studies investigating the relationship between AN and cytokine production. Data extracted from included studies related to population characteristics (e.g. age, gender, mean mBMI/%IBW), cytokine measurement and relevant findings. Confounding factors (e.g. smoking status, co-morbid mental illness, menstruation status) were also collected. RESULTS: 36 studies were eligible for this systematic review of which the majority were conducted in Europe (77.8%) and involved female subjects (97.2%). Those with AN ranged in age from 13 to 47 years and had an illness duration of 3 months to 24 years. 15 candidate cytokines and 3 receptors were identified (TNF-alpha, IL-6, IL-1B, CRP, IL-2, IL-7, IL-10, IFN-γ, TNF-R2, IL-1 α, IL-15, TNF-R1, IL-17, IL-18, TGF-B1, IL-12, IL-6R and TGF-B2) exploring in-vivo levels in patients with AN and comparing to controls. TNF-alpha and IL-6 were the most extensively studied with IL-6 being significantly elevated in 4 out of 8 (50%) of longitudinal studies when comparing AN patients at baseline compared to post weight restoration. Following weight restoration, there was no difference in IL-6 levels when comparing to HC in 7 of 8 (87.5%) longitudinal studies examined. CONCLUSIONS: The most promising cytokine potentially involved in the pathogenesis of AN appears to be IL-6, and possibly TNF-alpha pathways. The heterogeneity of clinical and methodology factors impedes the generalizability of results. Future studies may wish to address these methodological shortcomings as alterations in cytokine levels in AN could act as therapeutic targets assisting with weight restoration and psychopathology and may offer diagnostic potential.

Long-term follow-up of bilateral gracilis reconstruction following extra-levator abdominoperineal excision.

INTRODUCTION: Colorectal operations such as an extra-levator abdominoperineal (elAPE) excision for locally advanced or recurrent cancer create a significant perineal tissue deficit. Options for perineal reconstruction include bilateral pedicled gracilis muscle flaps (BPGMF). Fashioning the gracili into a 'weave' creates a muscular sling that supports pelvic contents and is a novel technique. Our series reports the outcomes of the BPGMF in 50 patients undergoing surgery for pelvic cancer. METHOD: This is a retrospective, single-centre study of patients undergoing reconstruction of perineal defects using BPGMF. All surgeries took place between January 2008 and February 2021. The primary outcome measured was perineal wound healing. The secondary outcomes measured were complications of surgical sites and length of hospital stay (short term), flap integrity on follow-up imaging and functional outcomes (long term). RESULTS: Fifty patients underwent perineal reconstruction using BPGMF (26 males). The median age was 62 years. The 30-day mortality was 2% (n = 1). The average follow-up period was 2 years. Complete perineal wound healing was 86% (42/49) at outpatient follow-up. Complication rates for the donor site and reconstructed site were 14% and 22%, respectively. Complications included infection (2% donor site, 12% perineum), haematoma (4% donor site), dehiscence (2% donor site, 4% perineum) and seroma (3% donor site, 2% perineum). CONCLUSION: BPGMF offers a reliable and technically simple muscle flap to reconstruct large perineal defects. The muscle flap integrity appears maintained on follow-up imaging despite a lack of flap monitoring tools. This cohort had minimal functional impairment following BPGMF.

Synovial expression of Th17-related and cancer-associated genes is regulated by the arthritis severity locus Cia10.

We have previously identified Cia10 as an arthritis severity and articular damage quantitative trait locus. In this study, we used Illumina RatRef-12 microarrays to analyze the expression of 21,922 genes in synovial tissues from arthritis-susceptible DA and arthritis-protected DA.ACI(Cia10) congenics with pristane-induced arthritis. 310 genes had significantly different expression. The genes upregulated in DA, and reciprocally downregulated in DA.ACI(Cia10) included IL-11, Ccl12 and Cxcl10, as well as genes implicated in Th17 responses such as IL-17A, IL-6, Ccr6, Cxcr3 and Stat4. Suppressors of immune responses Tgfb and Vdr, and inhibitors of oxidative stress were upregulated in congenics. There was an over-representation of genes implicated in cancer and cancer-related phenotypes such as tumor growth and invasion among the differentially expressed genes. Cancer-favoring genes like Ctsd, Ikbke, and Kras were expressed in increased levels in DA, whereas inhibitors of cancer phenotypes such as Timp2, Reck and Tgfbr3 were increased in DA.ACI(Cia10). These results suggest that Cia10 may control arthritis severity, synovial hyperplasia and joint damage via the regulation of the expression of cancer-related genes, inflammatory mediators and Th17-related markers. These new findings have the potential to generate new targets for therapies aimed at reducing arthritis severity and joint damage in rheumatoid arthritis.

Long-term use of the CentriMag® Ventricular Assist System as a right ventricular assist device: a case report.

Right ventricular failure (RVF) following implantation of a left ventricular assist system (LVAS) is associated with high morbidity and mortality.( 1-4 ) Numerous centers have reported short-term use of the CentriMag (®) Ventricular Assist System (CVAS) (Levitronix LLC, Waltham, MA) for treatment of cardiogenic shock, decompensated heart failure and right ventricular failure (RVF) following LVAS implantation.( 5-9 ) The present report reviews the clinical course of a patient requiring long-term right ventricular support utilizing the CVAS, following a HeartMate (®) II LVAS (Thoratec Corp. Pleasanton, CA) implantation. Elevated cytotoxic antibody levels complicated the patient's treatment plan by precluding orthotropic heart transplantation. The CVAS operated for 304 days without mechanical difficulty until replaced with the HeartWare (®) Ventricular Assist System (HeartWare Inc. Miramar, FL).

Safety and efficacy of multipotent adult progenitor cells in acute respiratory distress syndrome (MUST-ARDS): a multicentre, randomised, double-blind, placebo-controlled phase 1/2 trial.

PURPOSE: Bone marrow-derived, allogeneic, multipotent adult progenitor cells demonstrated safety and efficacy in preclinical models of acute respiratory distress syndrome (ARDS). METHODS: This phase 1/2 trial evaluated the safety and tolerability of intravenous multipotent adult progenitor cells in patients with moderate-to-severe ARDS in 12 UK and USA centres. Cohorts 1 and 2 were open-label, evaluating acute safety in three subjects receiving 300 or 900 million cells, respectively. Cohort 3 was a randomised, double-blind, placebo-controlled parallel trial infusing 900 million cells (n = 20) or placebo (n = 10) within 96 h of ARDS diagnosis. Primary outcomes were safety and tolerability. Secondary endpoints included clinical outcomes, quality of life (QoL) and plasma biomarkers. RESULTS: No allergic or serious adverse reactions were associated with cell therapy in any cohort. At baseline, the cohort 3 cell group had less severe hypoxia. For cohort 3, 28-day mortality was 25% for cell vs. 45% for placebo recipients. Median 28-day free from intensive care unit (ICU) and ventilator-free days in the cell vs. placebo group were 12.5 (IQR 0,18.5) vs. 4.5 (IQR 0,16.8) and 18.5 (IQR 0,22) vs. 6.5 (IQR 0,18.3), respectively. A prospectively defined severe ARDS subpopulation (PaO2/FiO2 < 150 mmHg (20 kPa); n = 16) showed similar trends in mortality, ICU-free days and ventilator-free days favouring cell therapy. Cell recipients showed greater recovery of QoL through Day 365. CONCLUSIONS: Multipotent adult progenitor cells were safe and well tolerated in ARDS. The clinical outcomes warrant larger trials to evaluate the therapeutic efficacy and optimal patient population.

Autism severity is associated with child and maternal MAOA genotypes.

Autism severity is associated with child and maternal MAOA genotypes. We replicated and extended a previously reported association between autism severity and a functional polymorphism in the monoamine oxidase A (MAOA) promoter region, MAOA-uVNTR, in a sample of 119 males, aged 2-13 years, with autism spectrum disorder from simplex families. We demonstrated that (i) boys with the low activity 3-repeat MAOA allele had more severe sensory behaviors, arousal regulation problems, and aggression, and worse social communication skills than males with the high activity allele; and (ii) problems with aggression, as well as with fears and rituals, were modified by the mothers' genotype. Boys with the 4-repeat high activity allele who had homozygous 4-repeat mothers showed increased severity of these behaviors relative to those born to heterozygous mothers. These findings indicate the importance of considering maternal genotype in examining associations of MAOA and other genes with behavior in male offspring.

Anti-tumor efficacy of an MMAE-conjugated antibody targeting cell surface TACE/ADAM17-cleaved Amphiregulin in breast cancer.

BACKGROUND: The Epidermal Growth Factor Receptor (EGFR) ligand, Amphiregulin (AREG), is a key proliferative effector of estrogen receptor signaling in breast cancer and also plays a role in other malignancies. AREG is a single-pass transmembrane protein proteolytically processed by TACE/ADAM17 to release the soluble EGFR ligand, leaving a residual transmembrane stalk that is subsequently internalized. METHODS: Using phage display, we identified antibodies that selectively recognize the residual transmembrane stalk of cleaved AREG. Conjugation with fluorescence labels and monomethyl auristatin E (MMAE) was used to study their intracellular trafficking and anti-cancer effects, respectively. RESULTS: We report the development of an antibody-drug conjugate (ADC), GMF-1A3-MMAE, targeting an AREG neo-epitope revealed following ADAM17-mediated cleavage. The antibody does not interact with uncleaved AREG, providing a novel means of targeting cells with high rates of AREG shedding. Using fluorescent dye conjugation, we demonstrated that the antibody is internalized by cancer cells in a manner dependent on the presence of cell surface cleaved AREG. Antibodies conjugated with MMAE were cytotoxic in vitro and induced rapid regression of established breast tumor xenografts in immunocompromised mice. We further demonstrate that these antibodies recognize the AREG neo-epitope in formalin-fixed, paraffin-embedded tumor tissue, suggesting their utility as a companion diagnostic for patient selection. CONCLUSIONS: This ADC targeting AREG has potential utility in the treatment of breast and other tumors in which proteolytic AREG shedding is a frequent event.

Survey of influenza A viruses circulating in wild birds in Canada 2005 to 2007.

A multi-agency, Canada-wide survey of influenza A viruses circulating in wild birds, coordinated by the Canadian Cooperative Wildlife Health Centre, was begun in the summer of 2005. Cloacal swab specimens collected from young-of-year ducks were screened for the presence of influenza A nucleic acids by quantitative, real-time reverse transcription-polymerase chain reaction (RRT-PCR). Specimens that produced positive results underwent further testing for H5 and H7 gene sequences and virus isolation. In addition to live bird sampling, dead bird surveillance based on RRT-PCR was also carried out in 2006 and 2007. The prevalence of influenza A viruses varied depending on species, region of the country, and the year of sampling, but generally ranged from 20% to 50%. All HA subtypes, with the exception of H14 and H15, and all NA subtypes were identified. The three most common HA subtypes were H3, H4, and H5, while N2, N6, and N8 were the three most common NA subtypes. H4N6, H3N2, and H3N8 were the three most common HA-NA combinations. The prevalence of H5 and H7 subtype viruses appears to have a cyclical nature.

Gamow's cyclist: a new look at relativistic measurements for a binocular observer.

The visualization of objects moving at relativistic speeds has been a popular topic of study since Special Relativity's inception. While the standard exposition of the theory describes certain shape-changing effects, such as the Lorentz-contraction, it makes no mention of how an extended object would appear in a snapshot or how apparent distortions could be used for measurement. Previous work on the subject has derived the apparent form of an object, often making mention of George Gamow's relativistic cyclist thought experiment. Here, a rigorous re-analysis of the cyclist, this time in three dimensions, is undertaken for a binocular observer, accounting for both the distortion in apparent position and the relativistic colour and intensity shifts undergone by a fast-moving object. A methodology for analysing binocular relativistic data is then introduced, allowing the fitting of experimental readings of an object's apparent position to determine the distance to the object and its velocity. This method is then applied to the simulation of Gamow's cyclist, producing self-consistent results.

Fitness Level Influences White Matter Microstructure in Postmenopausal Women.

Aerobic exercise has both neuroprotective and neurorehabilitative benefits. However, the underlying mechanisms are not fully understood and need to be investigated, especially in postmenopausal women, who are at increased risk of age-related disorders such as Alzheimer's disease and stroke. To advance our understanding of the potential neurological benefits of aerobic exercise in aging women, we examined anatomical and functional responses that may differentiate women of varying cardiorespiratory fitness using neuroimaging and neurophysiology. A total of 35 healthy postmenopausal women were recruited (59 ± 3 years) and cardiorespiratory fitness estimated (22-70 mL/kg/min). Transcranial magnetic stimulation was used to assess -aminobutyric acid (GABA) and glutamate (Glu) receptor function in the primary motor cortex (M1), and magnetic resonance spectroscopy (MRS) was used to quantify GABA and Glu concentrations in M1. Magnetic resonance imaging was used to assess mean cortical thickness (MCT) of sensorimotor and frontal regions, while the microstructure of sensorimotor and other white matter tracts was evaluated through diffusion tensor imaging. Regression analysis revealed that higher fitness levels were associated with improved microstructure in pre-motor and sensory tracts, and the hippocampal cingulum. Fitness level was not associated with MCT, MRS, or neurophysiology measures. These data indicate that, in postmenopausal women, higher cardiorespiratory fitness is linked with preserved selective white matter microstructure, particularly in areas that influence sensorimotor control and memory.

Genetic analysis of first-trimester miscarriages with a combination of cytogenetic karyotyping, microsatellite genotyping and arrayCGH.

Miscarriage is the spontaneous loss of an embryo or fetus before the 20th week of pregnancy. Most miscarriages occur before the end of the first trimester (<13 weeks). Although many risk factors relate to this occurrence, genetic factors play the most important role. Chromosomal abnormalities, including both numerical and structural anomalies, underlie the majority of miscarriages. In this study, we employed a comprehensive approach using cytogenetic karyotyping, polymerase chain reaction (PCR)-based genotyping, and microarray-based comparative genomic hybridization (arrayCGH) in combination to analyze chromosomal profiles of 115 first-trimester miscarriages of Chinese women. Seventy cases (61%) were found to have chromosomal anomalies, of which 90% were numerical and 10% were structural. Cytogenetic karyotyping identified 78.6% (55/70), PCR assays 2.9% (2 triploids), and arrayCGH 18.6% (13/70) of the anomalies. In this study, a microdeletion of 108 kb and four microduplications sizing from 300 to 1460 kb were observed. An advantage of using this combination approach is that microsatellite genotyping and arrayCGH can be accomplished in spite of culture failure and maternal cell contamination. In addition, arrayCGH can detect submicroscopic chromosomal anomalies and gene dosage alterations.