The relationship between visceral adiposity and cardiometabolic risk in Chinese women with polycystic ovary syndrome.

OBJECTIVE: To compare the extent to which visceral adiposity, as measured by mesenteric fat thickness, contribute to cardiometabolic risk, especially insulin resistance, in women with PCOS and healthy control. METHODS: This is a cross-sectional study with a total of 190 women with PCOS fulfilling the Rotterdam diagnostic criteria. Women without PCOS were recruited from a previous study, which comprised 416 healthy women controls with normal glucose tolerance. All subjects underwent OGTT, biochemical assessment, and sonographic assessment with measurements of mesenteric, preperitoneal and subcutaneous fat thickness. RESULTS: Mesenteric fat thickness was strongly correlated to cardiometabolic traits including blood pressure, fasting and 2-h glucose, triglycerides, HOMA-IR; and was negatively correlated to HDL-C in both cohorts (all p < 0.01). In PCOS, positive correlation was observed between mesenteric fat thickness and free androgen index (p < 0.01). Compared with controls, the regression line between mesenteric fat and HOMA-IR is much steeper in PCOS (p < 0.01). CONCLUSION: Women with PCOS remain more insulin resistant compared to controls at any given degree of visceral adiposity.

Smart Home-based IoT for Real-time and Secure Remote Health Monitoring of Triage and Priority System using Body Sensors: Multi-driven Systematic Review.

The Internet of Things (IoT) has been identified in various applications across different domains, such as in the healthcare sector. IoT has also been recognised for its revolution in reshaping modern healthcare with aspiring wide range prospects, including economical, technological and social. This study aims to establish IoT-based smart home security solutions for real-time health monitoring technologies in telemedicine architecture. A multilayer taxonomy is driven and conducted in this study. In the first layer, a comprehensive analysis on telemedicine, which focuses on the client and server sides, shows that other studies associated with IoT-based smart home applications have several limitations that remain unaddressed. Particularly, remote patient monitoring in healthcare applications presents various facilities and benefits by adopting IoT-based smart home technologies without compromising the security requirements and potentially large number of risks. An extensive search is conducted to identify articles that handle these issues, related applications are comprehensively reviewed and a coherent taxonomy for these articles is established. A total number of (n = 3064) are gathered between 2007 and 2017 for most reliable databases, such as ScienceDirect, Web of Science and Institute of Electrical and Electronic Engineer Xplore databases. Then, the articles based on IoT studies that are associated with telemedicine applications are filtered. Nine articles are selected and classified into two categories. The first category, which accounts for 22.22% (n = 2/9), includes surveys on telemedicine articles and their applications. The second category, which accounts for 77.78% (n = 7/9), includes articles on the client and server sides of telemedicine architecture. The collected studies reveal the essential requirement in constructing another taxonomy layer and review IoT-based smart home security studies. Therefore, IoT-based smart home security features are introduced and analysed in the second layer. The security of smart home design based on IoT applications is an aspect that represents a crucial matter for general occupants of smart homes, in which studies are required to provide a better solution with patient security, privacy protection and security of users' entities from being stolen or compromised. Innovative technologies have dispersed limitations related to this matter. The existing gaps and trends in this area should be investigated to provide valuable visions for technical environments and researchers. Thus, 67 articles are obtained in the second layer of our taxonomy and are classified into six categories. In the first category, 25.37% (n = 17/67) of the articles focus on architecture design. In the second category, 17.91% (n = 12/67) includes security analysis articles that investigate the research status in the security area of IoT-based smart home applications. In the third category, 10.44% (n = 7/67) includes articles about security schemes. In the fourth category, 17.91% (n = 12/67) comprises security examination. In the fifth category, 13.43% (n = 9/67) analyses security protocols. In the final category, 14.92% (n = 10/67) analyses the security framework. Then, the identified basic characteristics of this emerging field are presented and provided in the following aspects. Open challenges experienced on the development of IoT-based smart home security are addressed to be adopted fully in telemedicine applications. Then, the requirements are provided to increase researcher's interest in this study area. On this basis, a number of recommendations for different parties are described to provide insights on the next steps that should be considered to enhance the security of smart homes based on IoT. A map matching for both taxonomies is developed in this study to determine the novel risks and benefits of IoT-based smart home security for real-time remote health monitoring within client and server sides in telemedicine applications.

Presumptive migrating gall bladder mucocoele in two dogs with gall bladder rupture.

A 10-year-old neutered female soft-coated wheaten terrier and a 10-year-old, entire female Pomeranian were presented for vomiting and anorexia. Using ultrasound, an oval structure with a stellate, kiwifruit-like appearance typical of a gall bladder mucocoele was observed in the caudal abdomen of the soft-coated wheaten terrier and adjacent to the liver in the Pomeranian. There was also a moderate volume of abdominal effusion in both dogs. Cytology of the peritoneal fluid indicated a sterile exudative process but varied between the two dogs, with an absence of bile pigment in the soft-coated wheaten terrier and marked bile peritonitis in the Pomeranian. An entire free-floating ectopic mucocoele was confirmed via exploratory laparotomy with concomitant gall bladder rupture and common bile duct obstruction. Both dogs recovered completely after surgery. This is the first report of cases of gall bladder rupture with entire free-floating gall bladder mucocoeles in dogs.

Projecting the Burden of Chronic Kidney Disease in a Developed Country and Its Implications on Public Health.

BACKGROUND: Chronic Kidney Disease (CKD) is a major public health problem worldwide. There is limited literature on a model to project the number of people with CKD. This study projects the number of residents with CKD in Singapore by 2035 using a Markov model. METHODS: A Markov model with nine mutually exclusive health states was developed according to the clinical course of CKD, based on a discrete time interval of 1 year. The model simulated the transition of cohorts across different health states from 2007 to 2035 using prevalence, incidence, mortality, disease transition, and disease detection rates. RESULTS: From 2007 to 2035, the number of residents with CKD is projected to increase from 316,521 to 887,870 and the prevalence from 12.2% to 24.3%. Patients with CKD stages 1-2 constituted the largest proportion. The proportion of undiagnosed cases will decline from 72.1% to 56.4%, resulting from faster progression to higher CKD stages and its eventual detection. CONCLUSION: By 2035, about one-quarter of the Singapore residents are expected to have CKD. National policies need to focus on primary disease prevention and early disease detection to avoid delayed treatment of CKD which eventually leads to end-stage renal disease.

Radiographic and computed tomographic appearance of tracheal collapse with axial rotation in four dogs.

Tracheal collapse with axial rotation was diagnosed in four dogs. Radiographs showed increased tracheal dorsoventral height at the caudal cervical and thoracic inlet with and apparent intraluminal soft tissue opacity, mimicking an intraluminal tracheal foreign body. Computed tomography confirmed dorsoventral tracheal collapse with axial rotation in all dogs. Short-term outcome with medical treatment of all dogs was excellent.

Prevalence of the AMHR2 mutation in Miniature Schnauzers and genetic investigation of a Belgian Malinois with persistent Müllerian duct syndrome.

Persistent Müllerian duct syndrome (PMDS) is a sex-limited disorder in which males develop portions of the female reproductive tract. Important consequences of PMDS are cryptorchidism and its sequelae of infertility and increased risk of testicular cancer. Anti-Müllerian hormone (AMH) and its receptor (AMHR2) induce the regression of the Müllerian ducts in male embryos. In Miniature Schnauzer dogs, the genetic basis has been identified as an autosomal recessive nonsense mutation in AMHR2, but the allele frequency of the mutation is unknown. Thus, the primary objective of this study was to estimate the prevalence of the AMHR2 mutation in North American Miniature Schnauzers, in order to ascertain the value of genetic testing in this breed. An additional objective was to determine whether mutations in AMH or AMHR2 were responsible for PMDS in a Belgian Malinois; this would aid development of a genetic test for the Belgian Malinois breed. Genomic DNA from 216 Miniature Schnauzers (including one known PMDS case) was genotyped for the AMHR2 mutation, and DNA from a single PMDS-affected Belgian Malinois was sequenced for all coding exons of AMH and AMHR2. The Miniature Schnauzer cohort had an AMHR2 mutation allele frequency of 0.16 and a carrier genotypic frequency of 0.27. The genetic basis for PMDS in the Belgian Malinois was not determined, as no coding or splicing mutations were identified in either AMH or AMHR2. These findings support a benefit to AMHR2 mutation testing Miniature Schnauzers used for breeding or with cryptorchidism.

Paternal age as an independent factor does not affect embryo quality and pregnancy outcomes of testicular sperm extraction-intracytoplasmic sperm injection in azoospermia.

This study was performed to evaluate the independent influence of paternal age affecting embryo development and pregnancy using testicular sperm extraction (TESE)-intracytoplasmic sperm injection (ICSI) in obstructive azoospermia (OA) and nonobstructive azoospermia (NOA). Paternal patients were divided into the following groups: ≤30 years, 31-35 years, 36-40 years, 41-45 years and ≥46 years. There were no differences in the rates of fertilisation or embryo quality according to paternal and maternal age. However, clinical pregnancy and implantation rates were significantly lower between those ≥46 years of paternal age compared with other age groups. Fertilisation rate was higher in the OA than the NOA, while embryo quality, pregnancy and delivery results were similar. Clinical pregnancy and implantation rates were significantly lower for patients ≥46 years of paternal age compared with younger age groups. In conclusion, fertilisation using TESE in azoospermia was not affected by the independent influence of paternal age; however, as maternal age increased concomitantly with paternal age, rates of pregnancy and delivery differed between those with paternal age <41 years and ≥46 years. Therefore, paternal age ≥46 years old should be considered when applying TESE-ICSI in cases of azoospermia, and patients should be advised of the associated low pregnancy rates.

Molecular characterization of glycation-associated skin ageing: an alternative skin model to study in vitro antiglycation activity of topical cosmeceutical and pharmaceutical formulations.

BACKGROUND: Glycation is a nonenzymatic reaction that cross-links a sugar molecule and protein macromolecule to form advanced glycation products (AGEs) that are associated with various age-related disorders; thus glycation plays an important role in skin chronological ageing. OBJECTIVES: To develop a novel in vitro skin glycation model as a screening tool for topical formulations with antiglycation properties and to further characterize, at the molecular level, the glycation stress-driven skin ageing mechanism. METHODS: The glycation model was developed using human reconstituted full-thickness skin; the presence of Nε -(carboxymethyl) lysine (CML) was used as evidence of the degree of glycation. Topical application of emulsion containing a well-known antiglycation compound (aminoguanidine) was used to verify the sensitivity and robustness of the model. Cytokine immunoassay, quantitative real-time polymerase chain reaction and histological analysis were further implemented to characterize the molecular mechanisms of skin ageing in the skin glycation model. RESULTS: Transcriptomic and cytokine profiling analyses in the skin glycation model demonstrated multiple biological changes, including extracellular matrix catabolism, skin barrier function impairment, oxidative stress and subsequently the inflammatory response. Darkness and yellowness of skin tone observed in the in vitro skin glycation model correlated well with the degree of glycation stress. CONCLUSIONS: The newly developed skin glycation model in this study has provided a new technological dimension in screening antiglycation properties of topical pharmaceutical or cosmeceutical formulations. This study concomitantly provides insights into skin ageing mechanisms driven by glycation stress, which could be useful in formulating skin antiageing therapy in future studies.

Progesterone Alters Kynurenine Pathway Activation in IFN-γ-Activated Macrophages - Relevance for Neuroinflammatory Diseases.

We have previously demonstrated that the kynurenine pathway (KP), the major biochemical pathway for tryptophan metabolism, is dysregulated in many inflammatory disorders that are often associated with sexual dimorphisms. We aimed to identify a potential functional interaction between the KP and gonadal hormones. We have treated primary human macrophages with progesterone in the presence and absence of inflammatory cytokine interferon-gamma (interferon-γ) that is known to be a potent inducer of regulating the KP enzyme. We found that progesterone attenuates interferon-γ-induced KP activity, decreases the levels of the excitotoxin quinolinic acid, and increases the neuroprotective kynurenic acid levels. We also showed that progesterone was able to reduce the inflammatory marker neopterin. These results may shed light on the gender disparity in response to inflammation.

An enzyme in the kynurenine pathway that governs vulnerability to suicidal behavior by regulating excitotoxicity and neuroinflammation.

Emerging evidence suggests that inflammation has a key role in depression and suicidal behavior. The kynurenine pathway is involved in neuroinflammation and regulates glutamate neurotransmission. In the cerebrospinal fluid (CSF) of suicidal patients, levels of inflammatory cytokines and the kynurenine metabolite quinolinic acid (QUIN), an N-methyl-d-aspartate receptor agonist, are increased. The enzyme amino-ß-carboxymuconate-semialdehyde-decarboxylase (ACMSD) limits QUIN formation by competitive production of the neuroprotective metabolite picolinic acid (PIC). Therefore, decreased ACMSD activity can lead to excess QUIN. We tested the hypothesis that deficient ACMSD activity underlies suicidal behavior. We measured PIC and QUIN in CSF and plasma samples from 137 patients exhibiting suicidal behavior and 71 healthy controls. We used DSM-IV and the Montgomery-Åsberg Depression Rating Scale and Suicide Assessment Scale to assess behavioral changes. Finally, we genotyped ACMSD tag single-nucleotide polymorphisms (SNPs) in 77 of the patients and 150 population-based controls. Suicide attempters had reduced PIC and a decreased PIC/QUIN ratio in both CSF (P<0.001) and blood (P=0.001 and P<0.01, respectively). The reductions of PIC in CSF were sustained over 2 years after the suicide attempt based on repeated measures. The minor C allele of the ACMSD SNP rs2121337 was more prevalent in suicide attempters and associated with increased CSF QUIN. Taken together, our data suggest that increased QUIN levels may result from reduced activity of ACMSD in suicidal subjects. We conclude that measures of kynurenine metabolites can be explored as biomarkers of suicide risk, and that ACMSD is a potential therapeutic target in suicidal behavior.

Kynurenines, Gender and Neuroinflammation; Showcase Schizophrenia.

Schizophrenia has a clear sexual dimorphism in age of onset and progression. The underlying mechanisms of this dimorphism are not known, but may be found in the interactions of sex hormones with the tryptophan catabolising kynurenine pathway. Schizophrenia is associated with general inflammation and disruption of glutamatergic and dopaminergic signalling. Metabolites of the kynurenine pathway have been shown to be immunomodulatory and have effects on glutamatergic and dopaminergic signalling. This review discusses the currently available literature on sex hormones and their effect on the kynurenine pathway in the context of the glutamatergic, dopaminergic and immunological features of schizophrenia.

The higher frequency of IgA deficiency among Swedish twins is not explained by HLA haplotypes.

Serum immunoglobulin A (IgA) concentrations were determined in 12 600 adult Swedish twins, applying a high-throughput reverse-phase protein microarray technique. The prevalence of IgA deficiency (IgAD) was found to be 1:241 in monozygotic (MZ) twins and 1:198 in dizygotic (DZ) twins. Hence, the prevalence in twins is markedly elevated as compared with the normal Swedish adult population (1:600). The twins did not show a difference in the frequency of HLA haplotypes in comparison with almost 40 000 healthy Swedish controls. As expected, the risk-conveying HLA alleles A*01, B*08 and DRB1*01 were overrepresented among the IgAD twins and were also associated with significantly lower mean serum IgA concentrations in the twin cohort. In contrast, significantly higher mean IgA concentrations were found among individuals carrying the protective HLA alleles B*07 and DRB1*15. Exome sequencing data from two MZ twin pairs discordant for the deficiency showed no differences between the siblings. Model fitting analyses derived a heritability of 35% and indicate that genetic influences are modestly important for IgAD. The probandwise concordance rates for IgAD were found to be 31% for MZ and 13% for DZ twins.

Factors associated with adherence to low-tidal volume strategy for acute lung injury and acute respiratory distress syndrome and their impacts on outcomes: an observational study and propensity analysis.

BACKGROUND: The purpose of this study was to investigate the factors affecting adherence to the low-tidal volume (LTV) strategy in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) and their impacts on outcomes. METHODS: This prospective observational study included 111 patients with ALI/ARDS admitted to six intensive care units between March 2010 and February 2011. The patients were divided into the LTV group, which received a TV ≤7.5 mL/kg predicted body weight (PBW), and the non-LTV group, which received a TV >7.5 mL/kg PBW. We studied the association of selected clinical factors and adherence to the LTV strategy, and evaluated their impacts on 28-day mortality and 1-year mortality by the propensity-match process. RESULTS: Adherence to the LTV strategy was only 44%, which was related to lung injury severity (odds ratio [OR]: 3.15, P=0.038), muscle relaxant use (OR: 3.28, P=0.031), and depth of sedation (OR: 0.65, P=0.008). Propensity score-based analysis showed that the LTV group had modestly better 28-day survival (P=0.081) and 1-year survival (P=0.067) than the non-LTV group. Moreover, muscle relaxant use was strongly associated with reducing the risk of death at both 28 days (hazard ratio [HR]: 0.122, 95% confidence interval [CI]: 0.027-0.542, P=0.006) and 1 year ([HR]: 0.111, 95% [CI]: 0.030-0.408, P=0.001). CONCLUSION: Adherence to the LTV strategy was strongly associated with the lung injury score, muscle relaxant use, and depth of sedation. Propensity score-based analysis showed that the use of LTV ventilation and muscle relaxants reduced 28-day and 1-year mortality in ALI/ARDS patients.

Isolation and characterization of free haem from the shell gland of quail and hen.

Free haem was isolated from the shell gland of the quail, Coturnix coturnix japonica, and of the fowl, Galinus domesticus, and characterized by HPLC-ESI-MS/MS. Quantification by HPLC gave values of 1.17-1.40 nmol/mg quail shell gland protein for haem, 1.66-2.17 nmol/mg protein for protoporphyrin and 0.25-0.40 nmol/mg protein for biliverdin. Possible implications of this previously unreported finding are discussed but they are not considered incompatible with the conclusion that all eggshell pigments are endogenously synthesized in the oviduct system.

Bilateral multiple cystic kidney disease and renal cortical abscess in a Boerboel.

Cystic renal disease is rare in dogs and although infected renal cysts have been reported in humans, no report could be found in dogs. A 58 kg, 5-year-old, castrated, male Boerboel presented with weight loss, pyrexia, lethargy and vomiting, 20 months after an incident of haematuria was reported. The initial ultrasonographic diagnosis was bilateral multiple renal cysts of unknown aetiology. The cysts had significantly increased in size over the 20-month period and some contained echogenic specks which could be related to infection, normal cellular debris or haemorrhage. In both kidneys the renal contours were distorted (the left more than the right). The abnormal shape of the left kidney was largely due to multiple cysts and a large crescent-shaped septate mass on the cranial pole of the kidney. Aspirates of the septate mass were performed (left kidney) and the cytology and culture were indicative of an abscess. It is suggested that the previous incident of haematuria provided a portal of entry for bacteria into the cysts resulting in renal cortical abscess formation.

Multiple displacement amplification for preimplantation genetic diagnosis of fragile X syndrome.

Preimplantation genetic diagnosis (PGD) has become an assisted reproductive technique for couples that have genetic risks. Despite the many advantages provided by PGD, there are several problems, including amplification failure, allele drop-out and amplification inefficiency. We evaluated multiple displacement amplification (MDA) for PGD of the fragile X syndrome. Whole genome amplification was performed using MDA. MDA products were subjected to fluorescent PCR of fragile X mental retardation-1 (FMR1) CGG repeats, amelogenin and two polymorphic markers. In the pre-clinical tests, the amplification rates of the FMR1 CGG repeat, DXS1215 and FRAXAC1 were 84.2, 87.5 and 75.0%, respectively, while the allele dropout rates were 31.3, 57.1 and 50.0%, respectively. In two PGD treatment cycles, 20 embryos among 30 embryos were successfully diagnosed as 10 normal embryos, four mutated embryos and six heterozygous carriers. Three healthy embryos were transferred to the uterus; however, no clinical pregnancy was achieved. Our data indicate that MDA and fluorescent PCR with four loci can be successfully applied to PGD for fragile X syndrome. Advanced methods for amplification of minuscule amounts of DNA could improve the sensitivity and reliability of PGD for complicated single gene disorders.

In vitro biocompatibility of chitosan porous skin regenerating templates (PSRTs) using primary human skin keratinocytes.

Biopolymer chitosan (beta-1,4-d-glucosamine) comprises the copolymer mixture of N-acetylglucosamine and glucosamine. The natural biocompatibility and biodegradability of chitosan have recently highlighted its potential use for applications in wound management. Chemical and physical modifications of chitosan influence its biocompatibility and biodegradability, but it is unknown as to what degree. Hence, the biocompatibility of the chitosan porous skin regenerating templates (PSRT 82, 87 and 108) was determined using an in vitro toxicology model at the cellular and molecular level on primary normal human epidermal keratinocytes (pNHEK). Cytocompatibility was accessed by using a 3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl tetrazolium bromide (MTT) assay from 24 to 72h. To assess the genotoxicity of the PSRTs, DNA damage to the pNHEK was evaluated by using the Comet assay following direct contact with the various PSRTs. Furthermore, the skin pro-inflammatory cytokines TNF-alpha and IL-8 were examined to evaluate the tendency of the PSRTs to provoke inflammatory responses. All PSRTs were found to be cytocompatible, but only PSRT 108 was capable of stimulating cell proliferation. While all of the PSRTs showed some DNA damage, PSRT 108 showed the least DNA damage followed by PSRT 87 and 82. PSRT 87 and 82 induced a higher secretion of TNF-alpha and IL-8 in the pNHEK cultures than did PSRT 108. Hence, based on our experiments, PSRT 108 is the most biocompatible wound dressing of the three tested.