Journal of Clinical Medicine

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Open AccessArticle

Quality of Life with Macular Degeneration Is Not as Dark as It May Seem: Patients’ Perceptions of the MacDQoL Questionnaire

by Lisa M. Ord, JoAnne Wright, Margaret M. DeAngelis and Michael Feehan

J. Clin. Med. 2015, 4(9), 1841-1852; https://doi.org/10.3390/jcm4091841 - 22 Sep 2015

Cited by 7 | Viewed by 4874

Abstract

To determine the perceived relevance and value of an individualized measure of the impact of macular degeneration on quality of life (QoL) for elderly people with Age-Related Macular Degeneration (AMD) in the USA, through the assessment of the suitability of the measure’s domains [...] Read more.

To determine the perceived relevance and value of an individualized measure of the impact of macular degeneration on quality of life (QoL) for elderly people with Age-Related Macular Degeneration (AMD) in the USA, through the assessment of the suitability of the measure’s domains and by gaining a deeper insight into the impact of AMD on patients’ QoL vis-á-vis these domains, community-dwelling older adults in the metropolitan Salt Lake City, Utah area were interviewed using the macular degeneration on quality of life (MacDQoL) instrument. Participants felt that the MacDQoL was a relevant instrument for use in this US study population, though it could be improved by adding items pertaining to transportation, and independent driving, in particular, as an important QoL indicator. The emerging theme from analysis of the respondent’s commentary was that, in spite of AMD, these respondents were committed to engage in, and enjoy life. This is an important concept for clinicians and those who offer support programs to integrate into their care planning and reinforce in messaging to patients with the condition. Full article

(This article belongs to the Special Issue Age-Related Macular Disease)

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Open AccessReview

Interrelation between Neuroendocrine Disturbances and Medical Complications Encountered during Rehabilitation after TBI

by Caroline I. E. Renner

J. Clin. Med. 2015, 4(9), 1815-1840; https://doi.org/10.3390/jcm4091815 - 22 Sep 2015

Cited by 17 | Viewed by 6990

Abstract

Traumatic brain injury is not a discrete event but an unfolding sequence of damage to the central nervous system. Not only the acute phase but also the subacute and chronic period after injury, i.e., during inpatient rehabilitation, is characterized by multiple neurotransmitter [...] Read more.

Traumatic brain injury is not a discrete event but an unfolding sequence of damage to the central nervous system. Not only the acute phase but also the subacute and chronic period after injury, i.e., during inpatient rehabilitation, is characterized by multiple neurotransmitter alterations, cellular dysfunction, and medical complications causing additional secondary injury. Neuroendocrine disturbances also influence neurological outcome and are easily overlooked as they often present with diffuse symptoms such as fatigue, depression, poor concentration, or a decline in overall cognitive function; these are also typical sequelae of traumatic brain injury. Furthermore, neurological complications such as hydrocephalus, epilepsy, fatigue, disorders of consciousness, paroxysmal sympathetic hyperactivity, or psychiatric-behavioural symptoms may mask and/or complicate the diagnosis of neuroendocrine disturbances, delay appropriate treatment and impede neurorehabilitation. The present review seeks to examine the interrelation between neuroendocrine disturbances with neurological complications frequently encountered after moderate to severe TBI during rehabilitation. Common neuroendocrine disturbances and medical complications and their clinical implications are discussed. Full article

(This article belongs to the Special Issue Neuroendocrine Disturbances after Brain Damage)

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Open AccessArticle

Bioinformatic Interrogation of 5p-arm and 3p-arm Specific miRNA Expression Using TCGA Datasets

by Wei-Ting Kuo, Ming-Wei Su, Yungling Leo Lee, Chien-Hsiun Chen, Chew-Wun Wu, Wen-Liang Fang, Kuo-Hung Huang and Wen-chang Lin

J. Clin. Med. 2015, 4(9), 1798-1814; https://doi.org/10.3390/jcm4091798 - 15 Sep 2015

Cited by 15 | Viewed by 7593

Abstract

MicroRNAs (miRNAs) play important roles in cellular functions and developmental processes. They are also implicated in oncogenesis mechanisms and could serve as potential cancer biomarkers. Using high-throughput miRNA sequencing information, expression of both the 5p-arm and 3p-arm mature miRNAs were demonstrated and generated [...] Read more.

MicroRNAs (miRNAs) play important roles in cellular functions and developmental processes. They are also implicated in oncogenesis mechanisms and could serve as potential cancer biomarkers. Using high-throughput miRNA sequencing information, expression of both the 5p-arm and 3p-arm mature miRNAs were demonstrated and generated from the single miRNA hairpin precursor. However, current miRNA annotations lack comprehensive 5p-arm/3p-arm feature annotations. Among known human mature miRNAs, only half of them are annotated with arm features. This generated ambiguous results in many miRNA-Sequencing (miRNA-Seq) studies. In this report, we have interrogated the TCGA (the Cancer Genome Atlas) miRNA expression datasets with an improved, fully annotated human 5p-arm and 3p-arm miRNA reference list. By utilizing this comprehensive miRNA arm-feature annotations, enhanced determinations and clear annotations were achieved for the miRNA isoforms (isomiRs) recognized from the sequencing reads. In the gastric cancer (STAD) dataset, as an example, 32 5p-arm/3p-arm OPEN ACCESS J. Clin. Med. 2015, 4 1799 specific miRNAs were found to be down-regulated and 24 5p-arm/3p-arm specific miRNAs were found to be up-regulated. We have further extended miRNA biomarker discoveries to additional TCGA miRNA-Seq datasets and provided extensive expression information on 5p-arm/3p-arm miRNAs across multiple cancer types. Our results identified several miRNAs that could be potential common biomarkers for human cancers. Full article

(This article belongs to the Special Issue MicroRNAs: Novel Biomarkers and Therapeutic Targets for Human Cancers)

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323 KiB

Open AccessReview

Hypothalamic Obesity in Craniopharyngioma Patients: Disturbed Energy Homeostasis Related to Extent of Hypothalamic Damage and Its Implication for Obesity Intervention

by Christian L. Roth

J. Clin. Med. 2015, 4(9), 1774-1797; https://doi.org/10.3390/jcm4091774 - 09 Sep 2015

Cited by 54 | Viewed by 10735

Abstract

Hypothalamic obesity (HO) occurs in patients with tumors and lesions in the medial hypothalamic region. Hypothalamic dysfunction can lead to hyperinsulinemia and leptin resistance. This review is focused on HO caused by craniopharyngiomas (CP), which are the most common childhood brain tumors of [...] Read more.

Hypothalamic obesity (HO) occurs in patients with tumors and lesions in the medial hypothalamic region. Hypothalamic dysfunction can lead to hyperinsulinemia and leptin resistance. This review is focused on HO caused by craniopharyngiomas (CP), which are the most common childhood brain tumors of nonglial origin. Despite excellent overall survival rates, CP patients have substantially reduced quality of life because of significant long-term sequelae, notably severe obesity in about 50% of patients, leading to a high rate of cardiovascular mortality. Recent studies reported that both hyperphagia and decreased energy expenditure can contribute to severe obesity in HO patients. Recognized risk factors for severe obesity include large hypothalamic tumors or lesions affecting several medial and posterior hypothalamic nuclei that impact satiety signaling pathways. Structural damage in these nuclei often lead to hyperphagia, rapid weight gain, central insulin and leptin resistance, decreased sympathetic activity, low energy expenditure, and increased energy storage in adipose tissue. To date, most efforts to treat HO have shown disappointing long-term success rates. However, treatments based on the distinct pathophysiology of disturbed energy homeostasis related to CP may offer options for successful interventions in the future. Full article

(This article belongs to the Special Issue Neuroendocrine Disturbances after Brain Damage)

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Open AccessReview

Non-Proteinuric Diabetic Nephropathy

by Nicolas Roberto Robles, Juan Villa and Roman Hernandez Gallego

J. Clin. Med. 2015, 4(9), 1761-1773; https://doi.org/10.3390/jcm4091761 - 07 Sep 2015

Cited by 53 | Viewed by 7725

Abstract

Diabetic nephropathy patients traditionally show significant macroalbuminuria prior to the development of renal impairment. However, this clinical paradigm has recently been questioned. Epidemiological surveys confirm that chronic kidney disease (CKD) diagnosed by a low glomerular filtration rate (GFR) is more common in diabetic [...] Read more.

Diabetic nephropathy patients traditionally show significant macroalbuminuria prior to the development of renal impairment. However, this clinical paradigm has recently been questioned. Epidemiological surveys confirm that chronic kidney disease (CKD) diagnosed by a low glomerular filtration rate (GFR) is more common in diabetic patients than in the non-diabetic population but a low number of patients had levels of proteinuria above that which traditionally defines overt diabetic nephropathy (>500 mg/g). The large number of patients with low levels of proteinuria suggests that the traditional clinical paradigm of overt diabetic nephropathy is changing since it does not seem to be the underlying renal lesion in most of diabetic subjects with CKD. Full article

(This article belongs to the Special Issue Diabetic Nephropathy)

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Open AccessReview

Lipidomics to Assess Omega 3 Bioactivity

by Francesco Visioli

J. Clin. Med. 2015, 4(9), 1753-1760; https://doi.org/10.3390/jcm4091753 - 07 Sep 2015

Cited by 5 | Viewed by 5144

Abstract

How can we resolve the conflict between the strong epidemiological evidence pointing to the usefulness of fish—and, thus, omega 3—consumption with the debacle of supplementation trials? One potential explanation is that the null results obtained thus far are the consequences of ill-contrived investigations [...] Read more.

How can we resolve the conflict between the strong epidemiological evidence pointing to the usefulness of fish—and, thus, omega 3—consumption with the debacle of supplementation trials? One potential explanation is that the null results obtained thus far are the consequences of ill-contrived investigations that do not allow us to conclude on the effects (or lack thereof) of omega 3 fatty acid supplementation. One potential solution is through the use of lipidomics, which should prove very useful to screen suitable patients and to correlate plasma (or red blood cells, or whole blood, or phospholipid) fatty acid profile with outcomes. This has never been done in omega 3 trials. The wise use of lipidomics should be essential part of future omega 3 trials and would help in untangling this current riddle. Full article

(This article belongs to the Special Issue Omega-3 Fatty Acids in Health and Disease)

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Open AccessReview

MicroRNAs and Osteolytic Bone Metastasis: The Roles of MicroRNAs in Tumor-Induced Osteoclast Differentiation

by Tadayoshi Kagiya

J. Clin. Med. 2015, 4(9), 1741-1752; https://doi.org/10.3390/jcm4091741 - 28 Aug 2015

Cited by 37 | Viewed by 9748

Abstract

Osteolytic bone metastasis frequently occurs in the later stages of breast, lung, and several other cancers. Osteoclasts, the only cells that resorb bone, are hijacked by tumor cells, which break down bone remodeling systems. As a result, osteolysis occurs and may cause patients [...] Read more.

Osteolytic bone metastasis frequently occurs in the later stages of breast, lung, and several other cancers. Osteoclasts, the only cells that resorb bone, are hijacked by tumor cells, which break down bone remodeling systems. As a result, osteolysis occurs and may cause patients to suffer bone fractures, pain, and hypercalcemia. It is important to understand the mechanism of bone metastasis to establish new cancer therapies. MicroRNAs are small, noncoding RNAs that are involved in various biological processes, including cellular differentiation, proliferation, apoptosis, and tumorigenesis. MicroRNAs have significant clinical potential, including their use as new therapeutic targets and disease-specific biomarkers. Recent studies have revealed that microRNAs are involved in osteoclast differentiation and osteolytic bone metastasis. In this review focusing on microRNAs, the author discusses the roles of microRNAs in osteoclastogenesis and osteolytic bone metastasis. Full article

(This article belongs to the Special Issue MicroRNAs: Novel Biomarkers and Therapeutic Targets for Human Cancers)

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115 KiB

Open AccessReview

Hypothalamic-Pituitary-Adrenal Axis Programming after Recurrent Hypoglycemia during Development

by Raghavendra Rao

J. Clin. Med. 2015, 4(9), 1729-1740; https://doi.org/10.3390/jcm4091729 - 28 Aug 2015

Cited by 10 | Viewed by 5115

Abstract

Permanent brain injury is a complication of recurrent hypoglycemia during development. Recurrent hypoglycemia also has adverse consequences on the neuroendocrine system. Hypoglycemia-associated autonomic failure, characterized by ineffective glucose counterregulation during hypoglycemia, is well described in children and adults on insulin therapy for diabetes [...] Read more.

Permanent brain injury is a complication of recurrent hypoglycemia during development. Recurrent hypoglycemia also has adverse consequences on the neuroendocrine system. Hypoglycemia-associated autonomic failure, characterized by ineffective glucose counterregulation during hypoglycemia, is well described in children and adults on insulin therapy for diabetes mellitus. Whether recurrent hypoglycemia also has a programming effect on the hypothalamus-pituitary-adrenal cortex (HPA) axis has not been well studied. Hypoglycemia is a potent stress that leads to increased glucocorticoid secretion in all age groups, including the perinatal period. Other conditions associated with exposure to excess glucocorticoid in the perinatal period have a programming effect on the HPA axis activity. Limited animal data suggest the possibility of similar programming effect after recurrent hypoglycemia in the postnatal period. The age at exposure to hypoglycemia likely determines the HPA axis response in adulthood. Recurrent hypoglycemia in the early postnatal period likely leads to a hyperresponsive HPA axis, whereas recurrent hypoglycemia in the late postnatal period lead to a hyporesponsive HPA axis in adulthood. The age-specific programming effects may determine the neuroendocrine response during hypoglycemia and other stressful events in individuals with history of recurrent hypoglycemia during development. Full article

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Open AccessArticle

MicroRNA-224 Induces G1/S Checkpoint Release in Liver Cancer

by Fangmei An, Alexandru V. Olaru, Esteban Mezey, Qing Xie, Ling Li, Klaus B. Piontek and Florin M. Selaru

J. Clin. Med. 2015, 4(9), 1713-1728; https://doi.org/10.3390/jcm4091713 - 26 Aug 2015

Cited by 30 | Viewed by 5027

Abstract

Profound changes in microRNA (miR) expression levels are frequently found in liver cancers compared to the normal liver. In this study, we evaluate the expression of miR-224 in human HCC and CCA, as well as its downstream targets and affected pathways. We show [...] Read more.

Profound changes in microRNA (miR) expression levels are frequently found in liver cancers compared to the normal liver. In this study, we evaluate the expression of miR-224 in human HCC and CCA, as well as its downstream targets and affected pathways. We show that miR-224 is upregulated in a large cohort of human CCA, similar to its upregulation in human HCC. For the purpose of studying the roles of miR-224 in HCC and CCA, we enforced miR-224 expression in cells. mRNA arrays followed by Ingenuity Pathway Analysis (IPA)-identified putative molecules and pathways downstream of miR-224. Phenotypically, we report that enforced expression of miR-224 increases the growth rate of normal cholangiocytes, CCA cell lines, and HCC cell lines. In addition, we identified, in an unbiased fashion, that one of the major biologic processes affected by miR-224 is Gap1 (G1) to Synthesis (S) transition checkpoint release. We next identified p21, p15, and CCNE1 as downstream targets of miR-224 and confirmed the coordinated downregulation results in the increased phosphorylation of Retinoblastoma (Rb) with resulting G1/S checkpoint release. Our data suggest that miR-224 is a master regulator of cell cycle progression, and that its overexpression results in G1/S checkpoint release followed by accelerated cell growth. Full article

(This article belongs to the Special Issue MicroRNAs: Novel Biomarkers for Liver Diseases)

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Open AccessReview

MicroRNAs in the Cholangiopathies: Pathogenesis, Diagnosis, and Treatment

by Maria Jose Lorenzo Pisarello, Lorena Loarca, Tommy Ivanics, Leslie Morton and Nicholas LaRusso

J. Clin. Med. 2015, 4(9), 1688-1712; https://doi.org/10.3390/jcm4091688 - 26 Aug 2015

Cited by 19 | Viewed by 6472

Abstract

The cholangiopathies are a group of liver diseases resulting from different etiologies but with the cholangiocyte as the primary target. As a group, the cholangiopathies result in significant morbidity and mortality and represent one of the main indications for liver transplant in both [...] Read more.

The cholangiopathies are a group of liver diseases resulting from different etiologies but with the cholangiocyte as the primary target. As a group, the cholangiopathies result in significant morbidity and mortality and represent one of the main indications for liver transplant in both children and adults. Contributing to this situation is the absence of a thorough understanding of their pathogenesis and a lack of adequate diagnostic and prognostic biomarkers. MicroRNAs are small non-coding RNAs that modify gene expression post-transcriptionally. They have been implicated in the pathogenesis of many diseases, including the cholangiopathies. Thus, in this review we provide an overview of the literature on miRNAs in the cholangiopathies and discuss future research directions. Full article

(This article belongs to the Special Issue MicroRNAs: Novel Biomarkers for Liver Diseases)

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Open AccessReview

Clinical Potential of microRNA-7 in Cancer

by Jessica L. Horsham, Felicity C. Kalinowski, Michael R. Epis, Clarissa Ganda, Rikki A. M. Brown and Peter J. Leedman

J. Clin. Med. 2015, 4(9), 1668-1687; https://doi.org/10.3390/jcm4091668 - 25 Aug 2015

Cited by 42 | Viewed by 6492

Abstract

microRNAs (miRNAs) are a family of short, non-coding RNA molecules that drive a complex network of post-transcriptional gene regulation by enhancing target mRNA decay and/or inhibiting protein synthesis from mRNA transcripts. They regulate genes involved in key aspects of normal cell growth, development [...] Read more.

microRNAs (miRNAs) are a family of short, non-coding RNA molecules that drive a complex network of post-transcriptional gene regulation by enhancing target mRNA decay and/or inhibiting protein synthesis from mRNA transcripts. They regulate genes involved in key aspects of normal cell growth, development and the maintenance of body homeostasis and have been closely linked to the development and progression of human disease, in particular cancer. Over recent years there has been much interest regarding their potential as biomarkers and as therapeutic agents or targets. microRNA-7 (miR-7) is a 23 nucleotide (nt) miRNA known primarily to act as a tumour suppressor. miR-7 directly inhibits a number of oncogenic targets and impedes various aspects of cancer progression in vitro and in vivo, however, some studies have also implicated miR-7 in oncogenic roles. This review summarises the role of miR-7 in cancer, its potential in miRNA-based replacement therapy and its capacity as both a diagnostic and prognostic biomarker. Full article

(This article belongs to the Special Issue MicroRNAs: Novel Biomarkers and Therapeutic Targets for Human Cancers)

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J. Clin. Med., Volume 4, Issue 9 (September 2015) – 11 articles , Pages 1668-1852

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