My recollections of Hubel and Wiesel and a brief review of functional circuitry in the visual pathway

The first paper of Hubel and Wiesel in The Journal of Physiology in 1959 marked the beginning of an exciting chapter in the history of visual neuroscience. Through a collaboration that lasted 25 years, Hubel and Wiesel described the main response properties of visual cortical neurons, the functional architecture of visual cortex and the role of visual experience in shaping cortical architecture. The work of Hubel and Wiesel transformed the field not only through scientific discovery but also by touching the life and scientific careers of many students. Here, I describe my personal experience as a postdoctoral student with Torsten Wiesel and how this experience influenced my own work.     

Dissociative Symptoms and Cortisol Responses to Recounting Traumatic Experiences Among Childhood Sexual Abuse Survivors with PTSD

ABSTRACT

This study examined dissociative symptoms in relation to changes in evening salivary cortisol levels after recounting traumatic experiences among 49 women with PTSD for child sexual abuse (CSA). Each woman was interviewed to describe her sexual abuse and was assessed on acute dissociative symptoms in response to a recent stressful event in the previous month. Salivary cortisol was assessed during the interview using saliva samples taken immediately before and after the interview. Changes in cortisol levels were measured at one hour, 24 hours, and 48 hours after the interview. Acute dissociative symptoms were related to salivary cortisol levels 24 hours after the interview, with high dissociators showing elevated levels compared to low dissociators. These results suggest that dissociative symptoms in response to recent life stress are associated with cortisol dysregulation among women with PTSD for CSA.     

Electronic patient records and the impact of the Internet

The term electronic patient record (EPR) means the electronic collection of clinical narrative and diagnostic reports specific to an individual patient. A true EPR should allow physicians and nurses to practice in a paperless fashion. The wide adoption of Internet technologies should allow truly distributed sharing of patient data across traditional organizational barriers. Hence, the meaning of an EPR, as a representation of documents, should be transformed into a collaborative environment that supports workflow, enables new care models and allows secure access to distributed health data. This paper reviews the current realization of EPRs in the context of paper-based medical records. The Internet architecture that Boston-based medical informatics researchers refer to as W3-EMRS is described in the context of a successful implementation of CareWeb at the Beth Israel Deaconess Medical center. Finally, we describe how this Internet-based approach can be extended beyond the boundaries of traditional care settings to help evolve new collaborative models of eHealth.     

Diabetic patients and the impact of renal transplantation

A series of diabetic patients being evaluated for renal transplantation or having already had the procedure were referred for psychiatric evaluation and treatment. The authors note the disparity between the expectations of patients before transplantation and their subsequent level of functioning. The development of depression and behavioral problems is discussed with particular attention to the relationship between the severity of diabetic complications and the presence of depressive symptoms. Treatment may include behavioral approaches for negativistic patients and administration of tricyclic antidepressants for depressed patients.     

Norovirus seasonality and the potential impact of climate change

Seasonal variation in norovirus infection is a recognized but poorly understood phenomenon. It is likely to be based on biological, environmental and behavioural factors that regulate transmission, virulence and persistence of the virions in host populations. Understanding the seasonal dependency of norovirus infection is an important step towards understanding its epidemiology, with subsequent implementation of efficient measures of surveillance and control. Whether or not climate change could influence the seasonal patterns of norovirus infection, by impacting on its transmission, geographic distribution and prevalence, has not yet been considered. This review addresses the question.     

Glyconutrients: the state of the science and the impact of glycomics

The glyconutrients are simple sugars that are best described as foods and nutritional supplements derived from foods or other plant sources. As such, no therapeutic claims can be made that they prevent or treat specific diseases, as specified by Food and Drug Administration regulations. Companies marketing such products must be careful not to overstate the potential of these products, particularly in relation to disease treatment. Biological effects of glyconutrients are described including biochemical, immunological, and medical areas.Much of the literature on the clinical use of glyconutrients, such as illustrated by the three studies above, has been inconclusive and preliminary. A number of case reports and small pilot studies for conditions such as Tay-Sachs disease,¹⁶ chronic fatigue syndrome and fibromyalgia,¹⁷ attention deficit hyperactivity disorder,¹⁸ diabetes,¹⁹ autoimmune disease,²⁰ inflammatory bowel disease and interstitial cystitis,²¹ and others have been reported. These provide intriguing leads for the future. Yet, the clinical science of glyconutrients is clearly in its infancy. Many studies suffer from methodological and statistical problems as well as the concerns that industry support may unduly influence researchers interested in this field. Publications are often in industry-sponsored journals, websites,²² specialized symposia,²³ and other rather narrow scientific venues, which are helpful in an emerging science but do not reach a broad audience of clinicians and scientists.That being said, we predict that the gap in the clinical translation of the basic science of glycobiology will narrow as more high-quality research is conducted and is published in peer-reviewed journals, and innovative, safe, and effective glyco-therapies for difficult-to-treat and/or chronic conditions is introduced.Further, as respected scientists increase their interest in the associations of oligosaccharides with disease mechanisms, substantial advances will occur in the design of carbohydrate-based therapies and diagnostic techniques. This will promote the expansion of future clinical research.^{24 and 25} For now, what can clearly be stated is that the safety of these products is high. Their effectiveness in the prevention and treatment of disease remains promising, yet unproven. As the fields of glycobiology and functional glycomics evolve, we expect to see more evidence for a wide variety of clinical applications, as well as wellness support by glyconutrients.     

Incivility in the workplace: incidence and impact

This study extends the literature on interpersonal mistreatment in the workplace by examining the incidence, targets, instigators, and impact of incivility (e.g., disrespect, condescension, degradation). Data were collected from 1,180 public-sector employees, 71% of whom reported some experience of workplace incivility in the previous 5 years. As many as one third of the most powerful individuals within the organization instigated these uncivil acts. Although women endured greater frequencies of incivility than did men, both genders experienced similarly negative effects on job satisfaction, job withdrawal, and career salience. Uncivil workplace experiences were also associated with greater psychological distress; however, indices of psychological and physical health were relatively unaffected. The authors discuss these findings in the context of organizational and cognitive stress theories.     

Hydrodynamic regulation of lymphatic transport and the impact of aging

To accomplish its normal roles in body fluid regulation/macromolecular homeostasis, immune function, and lipid absorption; the lymphatic system must transport lymph from the interstitial spaces, into and through the lymphatics, through the lymphatic compartment of the nodes, back into the nodal efferent lymphatics and eventually empty into the great veins. The usual net pressure gradients along this path do not normally favor the passive movement of lymph. Thus, lymph transport requires the input of energy to the lymph to propel it along this path. To do this, the lymphatic system uses a series of pumps to generate lymph flow. Thus to regulate lymph transport, both lymphatic pumping and resistance must be controlled. This review focuses on the regulation of the intrinsic lymph pump by hydrodynamic factors and how these regulatory processes are altered with age. Intrinsic lymph pumping is generated via the rapid/phasic contractions of lymphatic muscle, which are modulated by local physical factors (pressure/stretch and flow/shear). Increased lymph pressure/stretch will generally activate the intrinsic lymph pump up to a point, beyond which the lymph pump will begin to fail. The effect of increased lymph flow/shear is somewhat more complex, in that it can either activate or inhibit the intrinsic lymph pump, depending on the pattern and magnitude of the flow. The pattern and strength of the hydrodynamic regulation of the lymph transport is different in various parts of the lymphatic tree under normal conditions, depending upon the local hydrodynamic conditions. In addition, various pathophysiological processes can affect lymph transport. We have begun to evaluate the influence of the aging process on lymphatic transport characteristics in the rat thoracic duct. The pressure/stretch-dependent activation of intrinsic pumping is significantly impaired in aged rat thoracic duct (TD) and the flow/shear-dependent regulatory mechanisms are essentially completely lacking. The loss of shear-dependent modulation of lymphatic transport appears to be related to a loss of normal eNOS expression and a large rise in iNOS expression in these vessels. Therefore, aging of the lymph transport system significantly impairs its ability to transport lymph. We believe this will alter normal fluid balance as well as negatively impact immune function in the aged animals. Further studies are needed to detail the mechanisms that control and alter lymphatic transport during normal and aged conditions.     

Asymmetry of stem cell fate and the potential impact of the niche

Asymmetric cell division is a common concept to explain the capability of stem cells to simultaneously produce a continuous output of differentiated cells and to maintain their own population of undifferentiated cells. Whereas for some stem cell systems, an asymmetry in the division process has explicitly been demonstrated, no evidence for such a functional asymmetry has been shown for hematopoietic stem cells (HSC) so far. This raises the question regarding whether asymmetry of cell division is a prerequisite to explain obvious heterogeneity in the cellular fate of HSC. Through the application of a mathematical model based on self-organizing principles, we demonstrate that the assumption of asymmetric stem cell division is not necessary to provide a consistent account for experimentally observed asymmetries in the development of HSC. Our simulation results show that asymmetric cell fate can alternatively be explained by a reversible expression of functional stem cell potentials, controlled by changing cell-cell and cell-microenvironment interactions. The proposed view on stem cell organization is pointing to the potential role of stem cell niches as specific signaling environments, which induce developmental asymmetries and therefore, generate cell fate heterogeneity. The self-organizing concept is fully consistent with the functional definition of tissue stem cells. It naturally includes plasticity phenomena without contradicting a hierarchical appearance of the stem cell population. The concept implies that stem cell fate is only predictable in a probabilistic sense and that retrospective categorization of stem cell potential, based on individual cellular fates, provides an incomplete picture.     

Estimating the burden and economic impact of pediatric genetic disease

PurposeTo identify the economic impact of pediatric patients with clinical indications of genetic disease (GD) on the US health-care system.MethodsUsing the 2012 Kids’ Inpatient Database, we identified pediatric inpatient discharges with International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes linked to genetic disease, including well-established genetic disorders, neurological diseases, birth defects, and other physiological or functional abnormalities with a genetic basis. Cohort characteristics and health-care utilization measures were analyzed. Discharges with a GD-associated primary diagnosis were used to estimate the minimum burden; discharges with GD-associated primary or secondary codes established the maximum burden.ResultsOf 5.85 million weighted discharges, 2.6–14% included GD-associated ICD-9-CM codes. For these discharges, mean total costs were $16,000–77,000 higher (P < 0.0001) in neonates and$12,000–17,000 higher (P < 0.0001) in pediatric patients compared with background, corresponding to significantly higher total charges and lengths of stay. Aggregate total charges for suspected GD accounted for $14 to $57 billion (11–46%) of the “national bill” for pediatric patients in 2012.ConclusionPediatric inpatients with diagnostic codes linked to genetic disease have a significant and disproportionate impact on resources and costs in the US health-care system.     

Medical education and its impact on the future of pathology

The impact of changes in medical education on the future of pathology are examined by analyzing how recommendations in the GPEP report may affect pathology practice. For pathologist teachers, there will be increasing involvement with students during the clinical years of the curriculum and emphasis on new course material particularly related to the problems of aging, environmental pathology, and principles of prevention. The hospital pathologist will have a leadership role in introducing computer technology and will become increasingly involved in ambulatory and outrearch services. Pathologists will become more involved in the continuing education of other physicians, particularly with emphasis on using the laboratory to solve specific problems utilizing new technologies, new areas of testing, and the pathologist as a consultant.