The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

Harrison's Principles of Internal Medicine

Articular cartilage is the highly specialized connective tissue of diarthrodial joints. Its principal function is to provide a smooth, lubricated surface for articulation and to facilitate the transmission of loads with a low frictional coefficient (Figure 1). Articular cartilage is devoid of blood vessels, lymphatics, and nerves and is subject to a harsh biomechanical environment. Most important, articular cartilage has a limited capacity for intrinsic healing and repair. In this regard, the preservation and health of articular cartilage are paramount to joint health.



Figure 1.

Gross photograph of healthy articular cartilage in an adult human knee.



Injury to articular cartilage is recognized as a cause of significant musculoskeletal morbidity. The unique and complex structure of articular cartilage makes treatment and repair or restoration of the defects challenging for the patient, the surgeon, and the physical therapist. The preservation of articular cartilage is highly dependent on maintaining its organized architecture.

/pdf/the-basic-science-of-articular-cartilage-structure-3mc2a5lzti.pdf

The basic science of articular cartilage: structure, composition, and function

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(11)60243-2.pdf

Osteoarthritis: an update with relevance for clinical practice

Context Duration of untreated psychosis (DUP) is the time from manifestation of the first psychotic symptom to initiation of adequate treatment. It has been postulated that a longer DUP leads to a poorer prognosis. If so, outcome might be improved through earlier detection and treatment. Objectives To establish whether DUP is associated with prognosis and to determine whether any association is explained by confounding with premorbid adjustment. Data Sources The CINAHL (Cumulative Index to Nursing and Allied Health), EMBASE, MEDLINE, and PsychLIT databases were searched from their inception dates to May 2004. Study Selection Eligible studies reported the relationship between DUP and outcome in prospective cohorts recruited during their first episode of psychosis. Twenty-six eligible studies involving 4490 participants were identified from 11 458 abstracts, each screened by 2 reviewers. Data Extraction Data were extracted independently and were checked by double entry. Sensitivity analyses were conducted excluding studies that had follow-up rates of less than 80%, included affective psychoses, or did not use a standardized assessment of DUP. Data Synthesis Independent meta-analyses were conducted of correlational data and of data derived from comparisons of long and short DUP groups. Most data were correlational, and these showed a significant association between DUP and several outcomes at 6 and 12 months (including total symptoms, depression/anxiety, negative symptoms, overall functioning, positive symptoms, and social functioning). Long vs short DUP data showed an association between longer DUP and worse outcome at 6 months in terms of total symptoms, overall functioning, positive symptoms, and quality of life. Patients with a long DUP were significantly less likely to achieve remission. The observed association between DUP and outcome was not explained by premorbid adjustment. Conclusions There is convincing evidence of a modest association between DUP and outcome, which supports the case for clinical trials that examine the effect of reducing DUP.

/pdf/association-between-duration-of-untreated-psychosis-and-3d33a68pa1.pdf

Association Between Duration of Untreated Psychosis and Outcome in Cohorts of First-Episode Patients: A Systematic Review

Longitudinal studies of cognition and functional outcome in schizophrenia: implications for MATRICS.

The sodium present in articular cartilage interacts with the negatively charged proteoglycan aggregates in the matrix of the cartilage. Sodium images of short echo time may be useful for detecting changes that occur in the proteoglycan content of the cartilage. Such changes are indicative of early osteoarthritic damage, for example. Using an asymmetric short echo technique, sodium images of high resolution and signal-to-noise ratio that demonstrate anatomic features of the cartilage are presented. These images were obtained with echo times as short as 1 msec, at an in-plane resolution of 39 microns by 117 microns and signal-to-noise ratios of up to 40:1.

High resolution, short echo time sodium imaging of articular cartilage.

Proton T1rho dispersion imaging is a recently described method for indirect detection of 17O. However, clinical implementation of this technique is hindered by the requirement for a high-amplitude spin-locking field (gammaB1 > 1 kHz) that exceeds current limitations in specific absorption rate (SAR). Here, a strategy is offered for circumventing high SAR in T1rho dispersion imaging of 17O through the use of low-amplitude off-resonance spin-locking pulses (gammaB1 < 300 Hz). Proton spin-lattice relaxation times in the off-resonance rotating frame were measured in H2(17)O-enriched tissue phantoms. On- and off-resonance T1rho dispersion imaging was implemented at 2 T using a spin-locking preparatory pulse cluster appended to a standard spin-echo sequence. On- and off-resonance dispersion images exhibited similar 17O-based image contrast. Magnetization transfer effects did not depend on 17O concentration and had no effect on image contrast. In conclusion, off-resonance proton T1rho dispersion imaging shows promise as a safe, sensitive technique for generating 17O-based T1rho contrast without exceeding SAR limitations.

Off-resonance proton T1rho dispersion imaging of 17O-enriched tissue phantoms.

Prior approaches have delivered 17O2 to a subject by inhalation, but the relationship between local signal changes and metabolism has been complicated by H217O created in non-cerebral tissues. During a brief pulse of 17O2 inhalation, this arterial input function for H217O is negligible due to convective transport delays. Additional delays in the arterial input function due to restricted diffusion of water makes pulsed inhalation of 17O2 even more effective. Accordingly, ventilator system are provided to deliver 17O2 as a brief pulse to a subject. Subsequent MR imaging demonstrates delayed appearance of H217O in the cerebral ventricles, suggesting that the arterial input function of H217O is delayed by restricted water diffusion in addition to convective transit delays. Delivery as a brief pulse therefore offers significant advantages in relating MR signal changes directly to metabolism.

Method and apparatus for providing pulses inhalation of 17O2 for magnetic resonance imaging of cerebral metabolism

The magnetization transfer ratio of the lumbar discs was spatially quantified from age-matched subjects and the nucleus pulposus magnetization transfer ratio was correlated with T2-weighted Pfirrmann grades. A moderate and significant linear correlation between magnetization transfer ratio and Pfirrmann grades was observed, suggesting that nucleus pulposus collagen relative density increases with degeneration. High-resolution axial magnetization transfer ratio maps revealed elevated magnetization transfer ratio in the nucleus pulposa of injured and heavily degenerated discs. In the injured disc, significant elevation in nucleus pulposa magnetization transfer ratio was not accompanied by significant decrease in disc height. This observation may suggest a possible increase in absolute collagen content, in addition to increased collagen relative density. In summary, magnetization transfer MRI of the disc may serve as a noninvasive diagnostic tool for disc degeneration, in addition to other MRI techniques specific to proteoglycan content.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/mrm.22533

Magnetization transfer ratio mapping of intervertebral disc degeneration.

Autism spectrum disorder (ASD) is a genetic heterogeneous neurodevelopmental disorder that is characterized by impairments in social interaction and speech development and is accompanied by stereotypical behaviors such as body rocking, hand flapping, spinning objects, sniffing and restricted behaviors. The considerable significance of the genetics associated with autism has led to the identification of many risk genes for ASD used for the probing of ASD specificity and shared cognitive features over the past few decades. Identification of ASD risk genes helps to unravel various genetic variants and signaling pathways which are involved in ASD. This review highlights the role of ASD risk genes in gene transcription and translation regulation processes, as well as neuronal activity modulation, synaptic plasticity, disrupted key biological signaling pathways, and the novel candidate genes that play a significant role in the pathophysiology of ASD. The current emphasis on autism spectrum disorders has generated new opportunities in the field of neuroscience, and further advancements in the identification of different biomarkers, risk genes, and genetic pathways can help in the early diagnosis and development of new clinical and pharmacological treatments for ASD.

Ravinder Reddy

Papers

High resolution, short echo time sodium imaging of articular cartilage.

Off-resonance proton T1rho dispersion imaging of 17O-enriched tissue phantoms.

Method and apparatus for providing pulses inhalation of 17O2 for magnetic resonance imaging of cerebral metabolism

Magnetization transfer ratio mapping of intervertebral disc degeneration.

Association of genes with phenotype in autism spectrum disorder.