Depression and Frailty in Patients With End‐Stage Liver Disease Referred for Transplant Evaluation

End‐stage liver disease (ESLD) patients are believed to have a high prevalence of depression, although mental health in ESLD has not been studied comprehensively. Further, the relationship between depression and severity of liver disease is unclear. Using baseline data from a large prospective cohort study (N = 500) of frailty in ESLD patients, we studied the association of frailty with depression. Frailty was assessed with the five‐component Fried Frailty Index. Patients were assigned a composite score of 0 to 5, with scores ≥3 considered frail. Depression was assessed using the 15‐question Geriatric Depression Scale, with a threshold of ≥6 indicating depression; 43.2% of patients were frail and 39.4% of patients were depressed (median score 4, range 0–15). In multivariate analysis, frailty was significantly associated with depression (odds ratio 2.78, 95% confidence interval 1.87–4.15, p < 0.001), whereas model for ESLD score was not associated with depression. After covariate adjustment, depression prevalence was 3.6 times higher in the most‐frail patients than the least‐frail patients. In conclusion, depression is common in ESLD patients and is strongly associated with frailty but not with severity of liver disease. Transplant centers should address mental health issues and frailty; targeted interventions may lower the burden of mental illness in this population.     

Mother's lifetime nutrition and the size, shape and efficiency of the placenta

Background

Studies have shown that the shape and size of the placenta at birth predict blood pressure in later life. The influences that determine placental morphology are largely unknown. We have examined the role of mother’s body size.

Methods

We studied 522 neonates who were born in a maternity hospital in Mysore, South India. The weight of the placenta and the length and breadth of its surface, were measured after delivery.

Results

Higher maternal fat mass predicted a larger placental surface (p = 0.02), while larger maternal head circumference predicted a more oval placental surface (p = 0.03). Higher maternal fat mass and larger maternal head circumference were associated with greater placental efficiency, indicated by lower ratios of the length (p = 0.0003 and p = 0.0001 respectively) and breadth (p = 0.0002 and p < 0.0001) of the surface to birthweight. In a sub-sample of 51 mothers whose own birthweight was available, higher maternal birthweight was related to lower ratios of the length and breadth of the surface to birthweight (p = 0.01 and 0.002). Maternal height was unrelated to placental size or shape.

Conclusions

Higher maternal fat mass, reflecting the mother’s current nutritional state, and larger maternal head circumference, reflecting the mother’s fetal/infant growth, are associated with changes in the shape and size of the placental surface and greater placental efficiency. We suggest that these associations reflect effects of the mother’s nutrition at different stages of her lifecourse on the development of the placenta and on materno-placento-fetal transfer of nutrients.     

Placental programming of blood pressure in Indian children

Aim: To determine whether the size and shape of the placental surface predict blood pressure in childhood. Methods: We studied blood pressure in 471 nine‐year‐old Indian children whose placental length, breadth and weight were measured in a prospective birth cohort study. Results: In the daughters of short mothers (相似文献   

Endoscopic skull base surgery for sinonasal malignancy

Management of malignant neoplasms of the sinonasal tract and skull base is hampered by the relative low incidence and pathologic diversity of patient presentations. Many studies have reported successful outcomes in the endoscopic management of malignancy since 1996, and these are summarized in this article. Nonsurgical adjuvant therapies are important for locoregional control because surgery occurs in a restricted anatomic space with close margins to critical structures, and distant disease is an ongoing concern in these disorders. There remains a need for collaborative consistent multicenter reporting, and international registries have been established to assist in such efforts.     

Opposing roles of mGluR8 in measures of anxiety involving non-social and social challenges

Metabotropic glutamate receptors (mGluRs) modulate glutamatergic and GABAergic neurotransmission. mGluR8, a member of group III receptors, is generally located presynaptically where it regulates neurotransmitter release. Previously we reported higher measures of anxiety in 6- and 12-month-old mGluR8^−/− male mice than age- and sex-matched wild-type mice and that acute pharmacological stimulation with the mGluR8 agonist (S)-3,4,-dicarboxyphenylglycine (DCPG) or the Positive Allosteric Modulator (PAM) AZ12216052 reduced measures of anxiety in wild-type mice. As in humans and animals, ageing is associated with enhanced measures of anxiety following non-social and social challenges, increased understanding of these measures and how to potentially modulate them is particularly important in the elderly. Here we determined whether the effects of AZ12216052 on measures of anxiety are mediated by mGluR8 using 24-month-old mGluR8^−/− and wild-type male mice. AZ12216052 also reduced measures of anxiety in the elevated zero maze and the acoustic startle response in mGluR8^−/− mice. The remaining anxiolytic effects of AZ12216052 in mGluR8^−/− mice might involve mGluR4, as the mGluR4 PAM VU 0155041 also reduced measures of anxiety in wild-type mice. In contrast, mGluR8^−/− mice show enhanced social interaction but AZ12216052 does not affect social interaction in wild-type mice. Thus, while mGluR8 is an attractive target to modulate measures of anxiety and social interaction, the effects of AZ12216052 on measures of anxiety likely also involve receptors other than mGluR8.     

Predictive molecular classifiers in colorectal cancer

The introduction of predictive molecular markers has radically enhanced the identification of which patients may benefit from a given treatment. Despite recent controversies, KRAS mutation is currently the most recognized molecular predictive marker in colorectal cancer (CRC), predicting efficacy of anti-epidermal growth factor receptor (anti-EGFR) antibodies. However, other relevant markers have been reported and claimed to identify patients that will benefit from anti-EGFR therapies. This group of markers includes BRAF mutations, PI3KCA mutations, and loss of PTEN expression. Similarly, molecular markers for cytotoxic agents' efficacy also may predict outcome in patients with CRC. This review aims to summarize the most important predictive molecular classifiers in patients with CRC and further discuss any inconsistent or conflicting findings for these molecular classifiers.     

Interleukin‐8 is associated with proliferation,migration, angiogenesis and chemosensitivity in vitro and in vivo in colon cancer cell line models

Interleukin‐8 (IL‐8), a chemokine with a defining CXC amino acid motif, is known to possess tumorigenic and proangiogenic properties. Overexpression of IL‐8 has been detected in many human tumors, including colorectal cancer (CRC), and is associated with poor prognosis. The goal of our study was to determine the role of IL‐8 overexpression in CRC cells in vitro and in vivo. We stably transfected the IL‐8 cDNA into two human colon cancer cell lines, HCT116 and Caco2, and selected IL‐8‐secreting transfectants. Real‐time RT‐PCR confirmed that IL‐8 mRNA was overexpressed in IL‐8 transfectants with 45‐ to 85‐fold higher than parental cells. The IL‐8‐transfected clones secreted 19‐ to 28‐fold more IL‐8 protein than control and parental cells as detected by ELISA. The IL‐8 transfectants demonstrated increased cellular proliferation, cell migration and invasion based on functional assays. Growth inhibition studies showed that IL‐8 overexpression lead to a significant resistance to oxaliplatin (p < 0.0001). Inhibition of IL‐8 overexpression with small interfering RNA reversed the observed increases in tumorigenic functions and oxaliplatin resistance, suggesting that IL‐8 not only provides a proliferative advantage but also promotes the metastatic potential of colon cancer cells. Using a tumor xenograft model, IL‐8‐expressing cells formed significantly larger tumors than the control cells with increased microvessel density. Together, these findings indicate that overexpression of IL‐8 promotes tumor growth, metastasis, chemoresistance and angiogenesis, implying IL‐8 to be an important therapeutic target in CRC.     

Current issues with standards in the measurement and documentation of human skeletal anatomy

Digital modeling of human anatomy has become increasingly important and relies on well-documented quantitative anatomy literature. This type of documentation is common for the spine and pelvis; however, significant issues exist due to the lack of standardization in measurement and technique. Existing literature on quantitative anatomy for the spine and pelvis of white adults (aged 18-65 years, separated into decadal categories) was reviewed from the disciplines of anatomy, manipulative therapy, anthropometrics, occupational ergonomics, biomechanics and forensic science. The data were unified into a single normative model of the sub-axial spine. Two-dimensional orthographic drawings were produced from the 590 individual measurements identified, which informed the development of a 3D digital model. A similar review of full range of motion data was conducted as a meta-analysis and the results were applied to the existing model, providing an inter-connected, articulated digital spine. During these data analysis processes several inconsistencies were observed accompanied by an evidential lack of standardization with measurement and recording of data. These have been categorized as: anatomical terminology; scaling of measurements; measurement methodology, dimension and anatomical reference positions; global coordinate systems. There is inconsistency in anatomical terminology where independent researchers use the same terms to describe different aspects of anatomy or different terms for the same anatomy. Published standards exist for measurement methods of the human body regarding spatial interaction, anthropometric databases, automotive applications, clothing industries and for computer manikins, but none exists for skeletal anatomy. Presentation of measurements often lacks formal structure in clinical publications, seldom providing geometric reference points, therefore making digital reconstruction difficult. Published quantitative data does not follow existing international published standards relating to engineering drawing and visual communication. Large variations are also evident in standards or guidelines used for global coordinate systems across biomechanics, ergonomics, software systems and 3D software applications. This paper identifies where established good practice exists and suggests additional recommendations, informing an improved communication protocol, to assist reconstruction of skeletal anatomy using 3D digital modeling.