Our objectives were to discuss a general overview on the description and recognition of heparin–induced thrombocytopenia (HIT) and present a critical review of the traditional and most recent advances in its pharmacotherapy. Computerized searches were done on MEDLINE and Iowa Drug Information Service (IDIS) databases from June 2001 until June 2007 and from May 2005 until May 2007, respectively. Search terms used included ‘heparin-induced thrombocytopenia’, ‘heparin-associated thrombocytopenia’, therapeutics, HIT, HAT. We largely selected publications within the timeframe above, but did not exclude commonly referenced and highly regarded older publications. The commonly referenced published articles were obtained through manual searches derived from bibliographic citations and retrievals from the authors’ personal files. Pertinent literatures (89 key articles) that were thought to have substantially contributed new information to the therapeutics of HIT within the last 6 years were identified, reviewed and presented. The following limits were used for the MEDLINE and IDIS searches: ‘human’, drug therapy’, ‘review’, ‘meta-analysis’, ‘clinical trial’, and case reports. The therapeutics of HIT is rapidly evolving and needs to consider an evidence – based approach. It is imperative that practitioners be aware of the associated risk and be up-to-date with the current advances in the management of this fatal clinical condition.

Osteogenesis imperfecta (OI) is characterized by susceptibility to bone fractures, with a severity ranging from subtle increase in fracture frequency to prenatal fractures. The first scientific description of OI dates from 1788. Since then, important milestones in OI research and treatment have, among others, been the classification of OI into 4 types (the ‘Sillence classification’), the discovery of defects in collagen type I biosynthesis as a cause of most cases of OI and the use of bisphosphonate therapy. Furthermore, in the past 5 years, it has become clear that OI comprises a group of heterogeneous disorders, with an estimated 90% of cases due to a causative variant in the COL1A1 or COL1A2 genes and with the remaining 10% due to causative recessive variants in the 8 genes known so far, or in other currently unknown genes. This review aims to highlight the current knowledge around the history, epidemiology, pathogenesis, clinical/radiological features, management, and future prospects of OI. The text will be illustrated with clinical descriptions, including radiographs and, where possible, photographs of patients with OI.

Objective. To evaluate the effectiveness of astragalus injection (a traditional Chinese patent medicine) for patients with renal damage induced by hypertension according to the available evidence. Methods. We searched MEDLINE, China National Knowledge Infrastructure (CNKI), Chinese VIP Information, China Biology Medicine (CBM), and Chinese Medical Citation Index (CMCI), and the date of search starts from the first of database to August 2011. No language restriction was applied. We included randomized controlled trials testing astragalus injection against placebo or astragalus injection plus antihypertensive drugs against antihypertensive drugs. Study selection, data extraction, quality assessment, and data analyses were conducted according to the Cochrane review standards. Results. 5 randomized trials (involving 429 patients) were included and the methodological quality was evaluated as generally low. The pooled results showed that astragalus injection was more effective in lowering β2-microglobulin (β2-MG), microalbuminuria (mAlb) compared with placebo, and it was also superior to prostaglandin in lowering blood urea nitrogen (BUN), creatinine clearance rate (Ccr). There were no adverse effects reported in the trials from astragalus injection. Conclusions. Astragalus injection showed protective effects in hypertensive renal damage patients...

Molecular imaging is used for the detection of biochemical processes through the development of target-specific contrast agents. Separately, modalities such as nuclear and near-infrared fluorescence (NIRF) imaging have been shown to non-invasively monitor disease. More recently, merging of these modalities has shown promise owing to their comparable detection sensitivity and benefited from the development of dual-labeled imaging agents. Dual-labeled agents hold promise for whole-body and intraoperative imaging and could bridge the gap between surgical planning and image-guided resection with a single, molecularly targeted agent. In this review, we summarized the literature for dual-labeled antibodies and peptides that have been developed and have highlighted key considerations for incorporating NIRF dyes into nuclear labeling strategies. We also summarized our findings on several commercially available NIRF dyes and offer perspectives for developing a toolkit to select the optimal NIRF dye and radiometal combination for multimodality imaging.

Functional neural connectivity is drawing increasing attention in neuroscience research. To infer functional connectivity from observed neural signals, various methods have been proposed. Among them, phase synchronization analysis is an important and effective one which examines the relationship of instantaneous phase between neural signals but neglecting the influence of their amplitudes. In this paper, we review the advances in methodologies of phase synchronization analysis. In particular, we discuss the definitions of instantaneous phase, the indexes of phase synchronization and their significance test, the issues that may affect the detection of phase synchronization and the extensions of phase synchronization analysis. In practice, phase synchronization analysis may be affected by observational noise, insufficient samples of the signals, volume conduction, and reference in recording neural signals. We make comments and suggestions on these issues so as to better apply phase synchronization analysis to inferring functional connectivity from neural signals.

Purpose. Chronic low back pain (LBP) is often characterized by both nociceptive and neuropathic components. While various monotherapies have been reported of only limited efficacy, combining drugs with different mechanisms of action and targets appears a rational approach. Aim of this systematic review is to assess the efficacy and safety of different combined pharmacological treatments, compared to monotherapy or placebo, for the pharmacological treatment of chronic LBP. Methods. Published papers, written or abstracted in English from 1990 through 2011, comparing combined pharmacological treatments of chronic LBP to monotherapy or placebo were reviewed. Results. Six articles met the inclusion criteria. Pregabalin combined with celecoxib or opioids was shown to be more effective than either monotherapy. Oxycodone-paracetamol versus previous treatments and tramadol-paracetamol versus placebo were also reported as effective, while morphine-nortriptyline did not show any benefit over any single agent. Conclusions. In spite of theoretical advantages of combined pharmacological treatments of chronic LBP, clinical studies are remarkably few. Available data show that combined therapy, including antinociceptive and antineuropathic agents is more effective than monotherapy...

Moral competence refers to the affective orientation to perform altruistic behaviors and the ability to judge moral issues logically. A five-stage theory of moral development is proposed. Both western and Chinese perspectives are incorporated in the elaboration of the characteristics of each stage. A brief review of the antecedents of moral competence is presented. The relationship between moral competence and adolescent developmental outcomes is also discussed. Some practical ways to promote moral competence are suggested. School-based programs may be effective in the promotion of moral competence provided it is based on all-round or whole-person development and the length of the program should be sufficiently long.

Lasmiditan is a novel selective 5-HT1F receptor agonist. It is both scientifically and clinically relevant to review whether a 5-HT1F receptor agonist is effective in the acute treatment of migraine. Two RCTs in the phase II development of lasmiditan was reviewed. In the intravenous placebo-controlled RCT, lasmiditan doses of 2.5–45 mg were used, and there was a linear association between headache relief (HR) rates and dose levels (P < 0.02). For lasmiditan 20 mg, HR was 64 % and for placebo it was 45 % (NS). In the oral placebo-controlled RCT, lasmiditan doses of 50, 100, 200 and 400 mg were used. For HR, all doses of lasmiditan were superior to placebo (P < 0.05). For lasmiditan 400 mg, HR was 64 % and it was 25 % for placebo. Adverse events (AEs) emerging from the treatment were reported by 22 % of the patients receiving placebo and by 65, 73, 87 and 87 % of patients receiving 50, 100, 200 and 400 mg, respectively. The majority of AEs after lasmiditan 100 and 400 mg were moderate or severe. For the understanding of migraine pathophysiology, it is very important to note that a selective 5-HT1F receptor agonist like lasmiditan is effective in the acute treatment of migraine. Thus, migraine can be treated with a drug that has no vasoconstrictor ability. While lasmiditan most likely is effective in the treatment of migraine attacks it had...

Introduction and Objective. Iatrogenic male stress urinary incontinence (SUI) affects a percentage of men undergoing urologic procedures with a significant impact on quality of life. The treatment of male SUI has evolved significantly with multiple current options for treatment available. The current paper discusses preoperative evaluation of male SUI, available surgical options with reported outcomes, and postoperative complication management. Methods. A pubMed review of available literature was performed and summarized on articles reporting outcomes of placement of the artificial urinary sphincter (AUS) or male slings including the bone anchored sling (BAS), retrourethral transobturator sling (RTS), adjustable retropubic sling (ARS), and quadratic sling. Results. Reported rates of success (variably defined) for BAS, RTS, ARS, and AUS are 36–67%, 9–79%, 13–100%, and 59–91% respectively. Complications reported include infection, erosion, retention, explantation, and transient pain. Male slings are more commonly performed in cases of low-to-moderate SUI with decreasing success with higher degrees of preoperative incontinence. Conclusions. An increasing number of options continue to be developed for the management of male SUI. While the AUS remains the gold-standard therapy for SUI...

The coronary slow flow phenomenon (CSFP) is a disease entity characterized by slow progression of angiographic contrast in the coronary arteries in the absence of stenosis in the epicardial vessels. CSFP has a diverse presentation from mild chest discomfort to ST-segment elevation myocardial infarction. It can also have severe morbidity and mortality implications and can significantly hamper the quality of life of those affected. In this paper we present two patients with CSFP highlighting the diverse spectrum of presentation. A concise review of the literature is also provided emphasizing the epidemiology, pathogenesis, diagnostic parameters, treatment modalities, and clinical significance of this phenomenon.

Reduced rates of consultations for otitis media after introduction of pneumococcal conjugate vaccines (PCVs) have been overinterpreted. This systematic review suggests that PCV is only somewhat modestly effective against all-cause otitis media.

Beta thalassemia major is an inherited disease resulting from reduction or total lack of beta globin chains. Patients with this disease need repeated blood transfusion for survival. This may cause oxidative stress and tissue injury due to iron overload, altered antioxidant enzymes, and other essential trace element levels. The aim of this review is to scrutinize the relationship between oxidative stress and serum trace elements, degree of damage caused by oxidative stress, and the role of antioxidant enzymes in beta thalassemia major patients. The findings indicate that oxidative stress in patients with beta thalassemia major is mainly caused by tissue injury due to over production of free radical by secondary iron overload, alteration in serum trace elements and antioxidant enzymes level. The role of trace elements like selenium, copper, iron, and zinc in beta thalassemia major patients reveals a significant change of these trace elements. Studies published on the status of antioxidant enzymes like catalase, superoxide dismutase, glutathione, and glutathione S-transferase in beta thalassemia patients also showed variable results. The administration of selective antioxidants along with essential trace elements and minerals to reduce the extent of oxidative damage and related complications in beta thalassemia major still need further evaluation.

A study has been conducted with the aim to provide researchers with general information on anti diabetic extracts based on relevant research articles collected from 34 reliable medical journals. The study showed that Asian and African continents have 56% and 17% share of the worldwide distribution of therapeutic herbal plants, respectively. In Asia, India and China are the leading countries in herbal plants research, and there has been an increase in medicinal research on plants extract for diabetes treatment since 1995 in these regions. The information collected shows that plant leaves are about 20% more favorable for storing active ingredients, as compared to other parts of herbal plants. A brief review on the extraction techniques for the mentioned parts is also included. Furthermore, the acting mechanisms for the anti diabetic activity were described, and the related active ingredients were identified. The findings reveal that most of the anti diabetic research is focused on the alteration of glucose metabolism to prevent diabetes.

Diabetic foot ulcerations are historically difficult to treat despite advanced therapeutic modalities. There are numerous modalities described in the literature ranging from noninvasive topical wound care to more invasive surgical procedures such as primary closure, skin flaps, and skin grafting. While skin grafting provides faster time to closure with a single treatment compared to traditional topical wound treatments, the potential risks of donor site morbidity and poor wound healing unique to the diabetic state have been cited as a contraindication to its widespread use. In order to garner clarity on this issue, a literature review was undertaken on the use of split-thickness skin grafts on diabetic foot ulcers. Search of electronic databases yielded four studies that reported split-thickness skin grafts as definitive means of closure. In addition, several other studies employed split-thickness skin grafts as an adjunct to a treatment that was only partially successful or used to fill in the donor site of another plastic surgery technique. When used as the primary closure on optimized diabetic foot ulcerations, split-thickness skin grafts are 78% successful at closing 90% of the wound by eight weeks.

The osseous pelvis is a well-recognized site of origin of numerous primary and secondary musculoskeletal tumors. The radiologic evaluation of a pelvic lesion often begins with the plain film and proceeds to computed tomography (CT), or magnetic resonance imaging (MRI) and possibly biopsy. Each of these modalities, with inherent advantages and disadvantages, has a role in the workup of pelvic osseous masses. Clinical history and imaging characteristics can significantly narrow the broad differential diagnosis for osseous pelvic lesions. The purpose of this review is to familiarize the radiologist with the presentation and appearance of some of the common benign neoplasms of the osseous pelvis and share our experience and approach in diagnosing these lesions.

Wound healing is a complex process involving a number of processes. Fetal regeneration has been shown to have a number of differences compared to scar-forming healing. This review discusses the number of differences identified in fetal regeneration. Understanding these differences may result in new therapeutic targets which may reduce or even prevent scarring in adult healing.

Childhood obesity is currently one of the most prevailing and challenging public health issues among industrialized countries and of international priority. The global prevalence of obesity poses such a serious concern that the World Health Organization (WHO) has described it as a “global epidemic.” Recent literature suggests that the genesis of the problem occurs in the first years of life as feeding patterns, dietary habits, and parental feeding practices are established. Obesity prevention evidence points to specific dietary factors, such as the promotion of breastfeeding and appropriate introduction of nutritious complementary foods, but also calls for attention to parental feeding practices, awareness of appropriate responses to infant hunger and satiety cues, physical activity/inactivity behaviors, infant sleep duration, and family meals. Interventions that begin at birth, targeting multiple factors related to healthy growth, have not been adequately studied. Due to the overwhelming importance and global significance of excess weight within pediatric populations, this narrative review was undertaken to summarize factors associated with overweight and obesity among infants and toddlers, with focus on potentially modifiable risk factors beginning at birth...

Hypertension is the most common medical disorder encountered during pregnancy. Hypertensive disorders are one of the major causes of pregnancy-related maternal deaths in the United States. We will present a comprehensive update of the literature pertinent to hypertension in pregnancy. The paper begins by defining and classifying hypertensive disorders in pregnancy. The normal vascular and renal physiological changes which occur during pregnancy are detailed. We will summarize the intriguing aspects of pathophysiology of preeclampsia, emphasizing on recent advances in this field. The existing diagnostic tools and the tests which have been proposed for screening preeclampsia are comprehensively described. We also highlight the short- and long-term implications of preeclampsia. Finally, we review the current management guidelines, goals of treatment and describe the potential risks and benefits associated with various antihypertensive drug classes. Preeclampsia still remains an enigma, and the present management focuses on monitoring and treatment of its manifestations. We are hopeful that this in depth critique will stimulate the blossoming research in the field and assist practitioners to identify women at risk and more effectively treat affected individuals.

The midbrain represents the uppermost portion of the brainstem, containing numerous important nuclei and white matter tracts, most of which are involved in motor control, as well as the auditory and visual pathways. Notable midbrain nuclei include the superior and inferior colliculus nuclei, red nucleus, substantia nigra, oculomotor nuclear complex, and trochlear nucleus. In addition, white matter tracts include the brachium conjunctivum, medial and lateral lemniscus, spinothalamic tracts, and the fiber tracts within the cerebral peduncles. Although neurologically vital, many of these small midbrain nuclei and white matter tracts are not easily individually identified on neuroimaging. However, given their diverse functions, midbrain pathology often leads to distinct clinical syndromes. A review and understanding of the location and relationships between the different midbrain nuclei and fiber tracts will allow more precise correlation of radiologic findings with patient pathology and symptomatology. Particular syndromes associated with midbrain pathology include the Weber, Claude, Benedikt, Nothnagel, and Parinaud syndromes. The oculomotor and trochlear cranial nerves also reside at this level. An understanding of their functions as well as their projected courses from the midbrain towards the eye allows identification of distinct locations which are particularly vulnerable to pathology.

Silent cerebral infarct (SCI) is the most common form of neurologic disease in children with sickle cell anemia (SCA). SCI is defined as abnormal magnetic resonance imaging (MRI) of the brain in the setting of a normal neurologic examination without a history or physical findings associated with an overt stroke. SCI occurs in 27% of this population before their sixth, and 37% by their 14th birthdays. In adults with SCA, the clinical history of SCI is poorly defined, although recent evidence suggests that they too may have ongoing risk of progressive injury. Risk factors for SCI include male sex, lower baseline hemoglobin concentration, higher baseline systolic blood pressure, and previous seizures. Specific morbidity associated with SCI includes a decrement in general intellectual abilities, poor academic achievement, progression to overt stroke, and progressive SCI. In addition, children with previous stroke continue to have both overt strokes and new SCI despite receiving regular blood transfusion therapy for secondary stroke prevention. Studies that only include overt stroke as a measure of CNS injury significantly underestimate the total cerebral injury burden in this population. In this review, we describe the epidemiology, natural history...