胆囊胆固醇性息肉的发病机制和诊治进展

胆固醇性息肉(CPs)是胆囊息肉最常见的类型,其发病机制尚未阐明。目前主要有3种学说:胆囊壁局部合成的胆固醇增加;从胆汁和(或)血液中摄取的胆固醇增加;胆囊黏膜细胞移出过量胆固醇的能力受损。本病临床表现无特异性,B超广泛应用于CPs的诊断,但不能作为确诊依据。CPs的治疗仍存在分歧,多数学者支持保守治疗。本文就CPs的发病机制、临床表现、诊断和治疗现状及其研究进展作一综述。     

Mycobacterium ulcerans infection: control, diagnosis, and treatment

The skin disease Buruli ulcer, caused by Mycobacterium ulcerans, is the third most common mycobacterial disease after tuberculosis and leprosy and mainly affects remote rural African communities. Although the disease is known to be linked to contaminated water, the mode of transmission is not yet understood, which makes it difficult to propose control interventions. The disease is usually detected in its later stages, when it has caused substantial damage and disability. Surgery remains the treatment of choice. Although easy and effective in the early stages of the disease, treatment requires extended excisions and long hospitalisation for the advanced forms of the disease. Currently, no antibiotic treatment has proven effective for all forms of M ulcerans infection and research into a new vaccine is urgently needed. While the scientific community works on developing non-invasive and rapid diagnostic tools, the governments of endemic countries should implement active case finding and health education strategies in their affected communities to detect the disease in its early stages. We review the diagnosis, treatment, and control of Buruli ulcer and list priorities for research and development.     

Anxiety of Alzheimer's disease: prevalence, and comorbidity.

BACKGROUND: Anxiety may be associated with psychiatric morbidity, disability, increased health care utilization, and mortality in Alzheimer's disease (AD) patients as it is in the general adult population. However, the phenomenology of anxiety symptoms in AD and its relationship to dementia progression, comorbid depression, and the presence of other problematic behaviors have not yet been examined. METHOD: Data on anxiety symptoms and their coexistence with other factors were obtained in 523 community-dwelling AD patients through interviews with their caregivers and direct physical examination. The prevalence of anxiety symptoms and their association to patient depression, other behavioral problems, gender, and age was investigated. RESULTS: Anxiety symptoms were common, occurring in 70% of subjects. Anxiety symptoms were significantly correlated with ADL impairment and other behavioral disturbances, including wandering, sexual misconduct, hallucinations, verbal threats, and physical abuse. Comorbidity of anxiety-depression was also prevalent: 54% of the sample had both anxiety and depression symptoms. ADL impairment and problem behaviors were significantly associated with comorbidity; however, the latter association was explained entirely by the presence of anxiety. CONCLUSION: Anxiety symptoms were common and significantly related to ADL and additional neuropsychiatric problems in this sample. These results indicate the need for additional research into the phenomenology of anxiety and comorbid anxiety-depression in AD and for the development and investigation of effective assessment and treatment of anxiety in AD clinical practice.     

Inflammation, Coagulation, and the Pathway to Frailty

There are inevitable physiologic changes associated with advancing age, yet for some people these changes are exaggerated, and as a result a phenotype emerges recognized as “frailty.” Why some people become frail and others do not remains incompletely understood. Although chronic illnesses are common among frail elderly persons, some will develop all of the phenotypic features without a diagnosed underlying disease. It has been recognized that certain proinflammatory cytokines and coagulation factors are elevated to a greater extent in those who are frail than in age-matched nonfrail individuals. In this review, we provide an overview of current research in the biology of frailty with particular emphasis on the role of inflammatory pathways and disordered coagulation in its pathogenesis.     

Temperature sensitivity of human perforin mutants unmasks subtotal loss of cytotoxicity,delayed FHL,and a predisposition to cancer

The pore-forming protein perforin is critical for defense against many human pathogens and for preventing a catastrophic collapse of immune homeostasis, manifested in infancy as Type 2 familial hemophagocytic lymphohistiocytosis (FHL). However, no evidence has yet linked defective perforin cytotoxicity with cancer susceptibility in humans. Here, we examined perforin function in every patient reported in the literature who lived to at least 10 years of age without developing FHL despite inheriting mutations in both of their perforin (PRF1) alleles. Our analysis showed that almost 50% of these patients developed at least 1 hematological malignancy in childhood or adolescence. The broad range of pathologies argued strongly against a common environmental or viral cause for the extraordinary cancer incidence. Functionally, what distinguished these patients was their inheritance of PRF1 alleles encoding temperature-sensitive missense mutations. By contrast, truly null missense mutations with no rescue at the permissive temperature were associated with the more common severe presentation with FHL in early infancy. Our study provides the first mechanistic evidence for a link between defective perforin-mediated cytotoxicity and cancer susceptibility in humans and establishes the paradigm that temperature sensitivity of perforin function is a predictor of FHL severity.     

Enigmatic,ultrasmall, uncultivated Archaea

Metagenomics has provided access to genomes of as yet uncultivated microorganisms in natural environments, yet there are gaps in our knowledge—particularly for Archaea—that occur at relatively low abundance and in extreme environments. Ultrasmall cells (<500 nm in diameter) from lineages without cultivated representatives that branch near the crenarchaeal/euryarchaeal divide have been detected in a variety of acidic ecosystems. We reconstructed composite, near-complete ~1-Mb genomes for three lineages, referred to as ARMAN (archaeal Richmond Mine acidophilic nanoorganisms), from environmental samples and a biofilm filtrate. Genes of two lineages are among the smallest yet described, enabling a 10% higher coding density than found genomes of the same size, and there are noncontiguous genes. No biological function could be inferred for up to 45% of genes and no more than 63% of the predicted proteins could be assigned to a revised set of archaeal clusters of orthologous groups. Some core metabolic genes are more common in Crenarchaeota than Euryarchaeota, up to 21% of genes have the highest sequence identity to bacterial genes, and 12 belong to clusters of orthologous groups that were previously exclusive to bacteria. A small subset of 3D cryo-electron tomographic reconstructions clearly show penetration of the ARMAN cell wall and cytoplasmic membranes by protuberances extended from cells of the archaeal order Thermoplasmatales. Interspecies interactions, the presence of a unique internal tubular organelle [Comolli, et al. (2009) ISME J 3:159–167], and many genes previously only affiliated with Crenarchaea or Bacteria indicate extensive unique physiology in organisms that branched close to the time that Cren- and Euryarchaeotal lineages diverged.     

Genetic epidemiology and public health: hope, hype, and future prospects

Genetic epidemiology is a rapidly expanding research field, but the implications of findings from such studies for individual or population health are unclear. The use of molecular genetic screening currently has some legitimacy in certain monogenic conditions, but no established value with respect to common complex diseases. Personalised medical care based on molecular genetic testing is also as yet undeveloped for common diseases. Genetic epidemiology can contribute to establishing the causal nature of environmentally modifiable risk factors, through the application of mendelian randomisation approaches and thus contribute to appropriate preventive strategies. Technological and other advances will allow the potential of genetic epidemiology to be revealed over the next few years, and the establishment of large population-based resources for such studies (biobanks) should contribute to this endeavour.     

Endobronchial stents: past, present, and future

Tracheobronchial prostheses, known as airway stents, are used to palliate the effects of large airway obstruction. The most common types of stents in current clinical use are made of silicone or metallic wire. An ideal stent should possess several characteristics: (1) it should be easy to insert and remove, if necessary; (2) it should be available in different sizes to match the obstruction; (3) once placed, it should maintain its position without migration; (4) it should be firm enough to resist compressive forces, yet have sufficient elasticity to conform to the airway contours; (5) it should be made of inert material, so as not to irritate the airway, precipitate infection, or promote granulation tissue; (6) it should exhibit the same characteristics of the normal airway so that mobilization of secretions is not impaired. We do not yet have an ideal airway stent that combines the advantages of silicone and metal stents. In this article, the advantages and disadvantages of currently available stents are reviewed, and some thoughts on the future development of airway stenting will be mentioned.     

A fast, high resolution, second-order central scheme for incompressible flows

A high resolution, second-order central difference method for incompressible flows is presented. The method is based on a recent second-order extension of the classic Lax-Friedrichs scheme introduced for hyperbolic conservation laws (Nessyahu H. & Tadmor E. (1990) J. Comp. Physics. 87, 408-463; Jiang G.-S. & Tadmor E. (1996) UCLA CAM Report 96-36, SIAM J. Sci. Comput., in press) and augmented by a new discrete Hodge projection. The projection is exact, yet the discrete Laplacian operator retains a compact stencil. The scheme is fast, easy to implement, and readily generalizable. Its performance was tested on the standard periodic double shear-layer problem; no spurious vorticity patterns appear when the flow is underresolved. A short discussion of numerical boundary conditions is also given, along with a numerical example.     

Accelerated wound healing: multidisciplinary advances in the care of venous leg ulcers

The etiologies of venous leg ulcers have been well known for millennia, and yet there remains no simple solution to this very common problem. Achieving closure of venous leg ulcers is often a lengthy process that is further complicated by the presence of significant comorbidities. The authors present data on healing venous leg ulcers in a cohort of 231 patients, most of whom had 1 or more complicating factors. Our multidisciplinary and aggressive approach to healing venous leg ulcers is described and has resulted in an average healing time of 29 days, a significantly shorter duration of treatment than the reported average of 6 months.     

Oversensing by single-chamber pacemakers: mechanisms, diagnosis, and treatment

Signals responsible for pacemaker oversensing may arise from the pacing system itself, P or T wave, concealed ventricular extrasystoles, skeletal muscle potentials, and distant electromagnetic fields. Oversensing is the most common cause of pacemaker pauses and a common clinical problem during follow-up of patients with implanted pulse generators. This article reviews the mechanisms and diagnosis of oversensing and the importance of multiprogrammability for its treatment.     

Fortuitously discovered liver lesions

The fortuitously discovered liver lesion is a common problem. Consensus might be expected in terms of its work-up, and yet there is none. This stems in part from the fact that there is no preventive campaign involving the early detection of liver tumors other than for patients with known liver cirrhosis and oncological patients. The work-up (detection and differential diagnosis) of liver tumors comprises theoretical considerations, history, physical examination, laboratory tests, standard ultrasound, Doppler ultrasound techniques, contrastenhanced ultrasound (CEUS), computed tomography and magnetic resonance imaging, as well as imageguided biopsy. CEUS techniques have proved to be the most pertinent method; these techniques became part of the clinical routine about 10 years ago in Europe and Asia and are used for a variety of indications in daily clinical practice. CEUS is in many cases the first and also decisive technical intervention for detecting and characterizing liver tumors. This development is reflected in many CEUS guidelines, e.g. , in the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) guidelines 2004, 2008 and 2012 as well as the recently published World Federation for Ultrasound in Medicine and Biology-EFSUMB guidelines 2012. This article sets out considerations for making a structured work-up of incidental liver tumors feasible.     

Cutaneous vasculitis, hypersensitivity vasculitis, erythema nodosum, and pyoderma gangrenosum

Cutaneous vasculitis encompasses a highly heterogeneous group of disorders of diverse etiology, pathogenesis, and clinical features. Recent reexamination of clinical pathologic features have yielded no insights assisting our understanding of current clinical classification schemes and strengthening our clinical approach. Erythema nodosum is a common cutaneous disorder for which new etiologies continue to be described. Pyoderma gangrenosum is an uncommon ulcerative cutaneous condition that remains a therapeutic problem.     

More Focus is Needed to Reduce Adverse Events for Diabetes Devices

Advances in devices for people with diabetes have demonstrated many improvements; yet, the number of adverse events has almost doubled from 2018 to 2019. It is a challenge to examine these events due to a difficult query tool on the FDA website. There are several possible reasons why effort is not devoted to decreasing the number of adverse events including the fact that user error is a common cause. This commentary serves to raise awareness of the adverse event problem.     

A switch in Notch gene expression parallels stem cell to endothelial transition in infantile hemangioma

Background  

Infantile hemangioma (IH) is the most common benign tumor of infancy, yet its pathogenesis is poorly understood. Notch family members are known to play a role in vascular development during embryogenesis and postnatal tumor angiogenesis, yet the role of Notch signaling in the pathogenesis of IH has not been investigated. This study aims to survey Notch expression in IH.     

Esophageal pH monitoring, indications, and methods

Symptomatic gastroesophageal reflux disease (GERD) is a common problem that affects a substantial proportion of the American population. It is estimated that the symptoms of GERD may afflict 40% to 45% of Americans each month. The diagnosis of GERD can be difficult, as its symptoms vary from typical symptoms like heartburn to atypical symptoms such as hoarseness, coughing, and chest pain. Most patients present with typical symptoms and are diagnosed with GERD if they respond to empiric trials of acid suppression. Many tests are available to help with diagnosing GERD in patients who either present with atypical symptoms or who do not respond to acid suppression; however, each test has its own shortcomings. The only test that directly measures whether acid is refluxing into the esophagus is the pH probe, but this test is uncomfortable for the patient, can be difficult to interpret, and may not be necessary in all cases. This article reviews the indications for pH monitoring, its technique, its advantages and limitations, and its role the diagnosis of GERD.     

Entomological studies on malaria in irrigated and non-irrigated areas of Thar desert, Rajasthan, India

BACKGROUND & OBJECTIVES: Malaria is the major health problem in western Rajasthan yet its vector fauna and transmission dynamics thereof is not understood properly. The present investigations report complete profile of qualitative and quantitative aspects of anopheline species occurring in different settings of desert ecosystem. METHODS: Area with irrigation through canal for more than 20 years (setting I), area with irrigation through canal for 10 years (setting II) and area without any irrigation (setting III) have been selected for studies. Species identification and their densities (per man hour) was made as per standard methods. RESULTS: In village of setting I, during rainy season, An. subpictus and An. stephensi were present while during winter season four species--An. subpictus, An. stephensi, An. culicifacies and An. annularis were collected. In all the villages of setting I, II and III no Anopheles mosquito was observed during summer season. In the villages of desert region without any irrigation facilities through any canal, the anopheline species were present only during rainy season. INTERPRETATION & CONCLUSION: An. stephensi is the major malaria vector of desert irrespective of whether the area is canal irrigated or not. During summer season absence of vector species in all the villages require further studies on micro-ecology of the species under desert conditions.     

Absence of indicators of the influence of its physicians on a society's health: Impact of physician care on society

There are no established indicators for measuring the influence of its private physicians on a society's health. For a brief period the age-adjusted death rate, an important indicator of the public health effort, also served to reflect a portion of the influence of the personal physician system. Particular medical interventions could be linked to specific sites in the pathogenesis of microbial disease in a way not yet permitted by the available knowledge of the common nonmicrobial diseases.Our national allocations for health cannot be made rationally until we develop indicators for measuring incremental investments in either system, but especially for the personal physician system. For death rates per se fail to accurately reflect the workings of this system which is concerned primarily with prolonging effective life by preserving or restoring function in an individual person.     

Carbohydrate-Deficient Transferrin as a Marker of Alcohol Abuse: Relationship to Alcohol Consumption, Severity of Liver Disease, and Fibrogenesis

Carbohydrate-deficient transferrin (CDT) measurements have been widely examined as a marker of excessive alcohol consumption, yet the information on the sensitivity of this method has remained controversial. In addition, little is known of the relationship of this marker and the severity of alcoholic liver disease (ALD). To clarify these Issues, we analyzed serum samples from 373 alcohol abusers, including 200 problem drinkers with no apparent liver pathology, 173 patients with clinical or morphological evidence of ALD, and 42 healthy controls. CDT was analyzed by anion-exchange chromatography followed by radioimmunoassay. At a specificity of 100%, the sensitivity of CDT was 36% in problem drinkers reporting a mean of 710 ± 80 (mean ± 2SE) g of ethanol/week, as compared with the sensitivities of 44% and 35% for γ-glutamyltranspeptidase (GGT) and mean corpuscular volume (MCV), respectively. In a subgroup of problem drinkers (n= 51) with the highest ethanol intakes (1160 ± 180 g of ethanol/week) and severe dependence, the sensitivity of CDT increased to 64%, compared with 55% for GGT and 39% for MCV. In ALD, the CDT values were significantly higher than in the alcoholics with nonliver pathology. However, when such patients were classified according to the clinical, laboratory, and morphological severity of liver disease, CDT was found to be primarily elevated in those with the early stage of ALD, such that there was a significant negative correlation between CDT and the combined morphological index of disease severity (r_s= -0.315, p < 0.05). ALD markers of fibrogenesis were elevated more frequently than CDT, showing significant positive correlations with the indices of disease severity. Current data indicates that, although CDT concentration correlates with the amount of alcohol consumed, it lacks diagnostic sensitivity in alcohol abusers consuming < 100 g of alcohol per day, thus hampering its use as a screen for consumption in community samples. The finding that CDT is increased in an early phase of ALD may prove to be of diagnostic value.