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Understanding the biomechanical behavior of the intervertebral disc is crucial for studying disease mechanisms and developing tissue engineering strategies for managing disc degeneration. We used synchrotron small-angle X-ray scattering to investigate how changes to collagen behavior contribute to alterations in the disc's ability to resist compression. Coccygeal motion segments from 6-month-old lean Sprague-Dawley rats ( n = 7 ) and diabetic obese University of California Davis type 2 diabetes mellitus (UCD-T2DM) rats ( n = 6 , diabetic for 68 ± 7 days) were compressed during simultaneous synchrotron scanning to measure collagen strain at the nanoscale (beamline 7.3.3 of the Advanced Light Source). After compression, the annulus fibrosus was assayed for nonenzymatic cross-links. In discs from lean rats, resistance to compression involved two main energy-dissipation mechanisms at the nanoscale: (1) rotation of the two groups of collagen fibrils forming the annulus fibrosus and (2) straightening (uncrimping) and stretching of the collagen fibrils. In discs from diabetic rats, both mechanisms were significantly impaired. Specifically, diabetes reduced fibril rotation by 31% and reduced collagen fibril strain by 30% (compared to lean discs). The stiffening of collagen fibrils in the discs from diabetic rats was consistent with a 31% higher concentration of nonenzymatic cross-links and with evidence of earlier onset plastic deformations such as fibril sliding and fibril-matrix delamination. These findings suggest that fibril reorientation, stretching, and straightening are key deformation mechanisms that facilitate whole-disc compression, and that type 2 diabetes impairs these efficient and low-energy elastic deformation mechanisms, thereby altering whole-disc behavior and inducing the earlier onset of plastic deformation., (© The Author(s) 2023. Published by Oxford University Press on behalf of National Academy of Sciences.)

Age and diabetes have long been known to induce an oxidative reaction between glucose and collagen, leading to the accumulation of advanced glycation end-products (AGEs) cross-links in collagenous tissues. More recently, AGEs content has been related to loss of bone quality, independent of bone mass, and increased fracture risk with aging and diabetes. Loss of bone quality is mostly attributed to changes in material properties, structural organization, or cellular remodeling. Though all these factors play a role in bone fragility disease, some common recurring patterns can be found between diabetic and age-related bone fragility. The main pattern we will discuss in this viewpoint is the increase of fibrillar collagen stiffness and loss of collagen-induced plasticity with AGE accumulation. This study focused on recent related experimental studies and discusses the correlation between fluorescent AGEs content at the molecular and fibrillar scales, collagen deformation mechanisms at the nanoscale, and resistance to bone fracture at the macroscale., Competing Interests: Conflicts of Interest: The authors declare that they have no conflicts of interest to report regarding the present study.

Current treatment options for allergic rhinoconjunctivitis include topical antihistamines, vasoconstrictors, mast cell stabilizers, intranasal corticosteroids (INCS), and nonsteroidal anti-inflammatory drugs that are generally used as a supplement to oral or intranasal therapies, necessitating the use of multiple treatments for the different symptoms of allergic rhinitis (AR). To assess the efficacy of INCS for ocular symptoms (OS) of AR. A search was performed of clinical trials (n = 32) from 1973 to 2009 of English articles (Medline, Embase, and PubMed) using "intranasal corticosteroid," "allergic rhinitis," "ocular symptoms," "allergic conjunctivitis," and "rhinoconjunctivitis" as key words. Quality assessment for the 32 eligible studies was performed using the Jadad score. Statistical analysis for continuous data was done by weighted mean difference or standardized mean difference. Thirty-two trials were included and separated into three different groups. The overall weighted mean was obtained from the Jadad score and came out to 9.29 (95% CI, 8.7-9.88). For meta-analysis for total OS scores and individual symptoms (10 parallel studies) the weighted mean was 10.17 (95% CI, 9.34-11). In the parallel studies, meta-analysis of individual symptoms (nine studies) gave a weighted mean of 10.09 (95% CI, 9.55-10.63). For eye symptoms but no individual symptoms (13 studies), the weighted mean was 8.56 (95% CI, 7.66-9.46). To date, clinical studies conducted statistically showed the efficacy of INCS on the OS of AR as evidenced by the meta-analysis results for the studies reporting total OSs.

In response to public concerns about the consequences of research misconduct, academic institutions have become increasingly cognizant of the need to implement comprehensive, effective training in the responsible conduct of research (RCR) for faculty, staff, students, and external collaborators. The ability to meet this imperative is challenging as universities confront declining financial resources and increasing complexity of the research enterprise. The authors describe the University of Pittsburgh's design, implementation, and evaluation of a Web-based, institution-wide RCR training program called Research and Practice Fundamentals (RPF). This project, established in 2000, was embedded in the philosophy, organizational structure, and technology developed through the Integrated Advanced Information Management Systems grant from the National Library of Medicine. Utilizing a centralized, comprehensive approach, the RPF system provides an efficient mechanism for deploying content to a large, diverse cohort of learners and supports the needs of research administrators by providing access to information about who has successfully completed the training. During its first 3 years of operation, the RPF served over 17,000 users and issued more than 38,000 training certificates. The 18 modules that are currently available address issues required by regulatory mandates and other content areas important to the research community. RPF users report high levels of satisfaction with content and ease of using the system. Future efforts must explore methods to integrate non-RCR education and training into a centralized, cohesive structure. The University of Pittsburgh's experience with the RPF demonstrates the importance of developing an infrastructure for training that is comprehensive, scalable, reliable, centralized, affordable, and sustainable.

Background: Stool-based DNA screening for colorectal cancer (CRC) was recently made available for use in daily clinical practice (PreGen-Plus). The main objectives of this study were to examine patients' screening experiences with stool DNA testing in routine clinical practice and the results of diagnostic colonoscopy in patients with an antecedent abnormal stool DNA test., Patients and Methods: Patients undergoing stool-based DNA testing were asked to complete and return via mail an anonymous 10-item questionnaire inquiring about their test-related experiences. Colonoscopy findings for all abnormal stool-based DNA tests were ascertained via a telephone survey of the ordering primary care clinicians' offices., Results: Patient survey responses were collected between August 2003 and July 2005 and reflect an 18% (1211 of 6730) response rate. The majority reported that the specimen collection process was very easy/easy to perform (87%), that they were very likely/likely to use the test again (91%), and that they had never been screened for CRC previously by any method (52%). Tests were ordered predominantly by the patient's primary care clinician (90%), including obstetrician/gynecologist providers. Colonoscopy findings from 69 of 159 patients with an antecedent abnormal stool DNA test screened with PreGen-Plus between August 2003 and July 2004 were available for review. An abnormal stool DNA test correlated with a colonoscopically demonstrable abnormality in 49% of cases (34 of 69). Abnormal findings, including CRC in 3 patients (4%; 1 with Dukes A and 2 with Dukes B disease), single or multiple adenomatous polyps in 23 patients (33%), hyperplastic polyps in 3 patients (4%), and colitis in 5 patients (7%). Colonoscopy was reported as negative in 51% of patients (35 of 69), including 2 cases (3%) with an altered BAT-26 microsatellite caused by a normal polymorphism., Conclusion: Stool DNA testing provides an acceptable noninvasive alternative for CRC screening that can identify early-stage CRCs and adenomatous polyps in routine clinical practice. Ongoing and broader surveys are indicated to support these early findings.

The scientific career of James Franck (26 August 1882-21 May 1964) spanned seven decades in which he was preoccupied with understanding the interaction of light with matter, starting with atoms and moving to the photosynthetic apparatus in green plants.

The occurrence of localized large clusters of colonic pseudopolyps in 4 patients is described. The underlying disease was chronic ulcerative colitis in 2 cases and granulomatous colitis in 2 others. Each lesion presented as a bulky polypoid mass causing partial or total occlusion of the transverse segment or splenic flexure of the colon. The radiographic and pathologic features of this rare entity are illustrated, and the previously reported 10 cases are briefly reviewed.

Seventy-four women enrolled in an in vitro fertilization (IVF) program had cytologic smears of the vagina, cervix and endometrium obtained at the time of embryo transfer (ET). Of these, 68 vaginal, 46 cervical and 25 endometrial smears were available for cytologic examination. Of the 68 vaginal smears, 4% showed a proliferative pattern, 40% were early secretory and 56% were advanced secretory. The 46 cervical smears demonstrated a delayed hormonal effect, with 70% showing a proliferative pattern, 23% early secretory and 7% advanced secretory cytology. Endometrial cells were obtained only when the Jones catheter, which has a side opening, was used. Twenty-two patients had both vaginal smears and suitable endometrial smears. Of these, 8 of the 9 patients with early secretory vaginal cytology had secretory endometrium while 10 of the 12 patients with mid-secretory vaginal cytology had secretory endometrium. The value of endometrial cytology in predicting conception following IVF-ET is unknown. It seems, however, that a good correlation exists between endometrial and vaginal cytology and that the latter may be of value as an additional, noninvasive tool for the evaluation of endometrial development.

Excessive blood loss can limit the area of burn excised per sitting, lead to selection of en bloc rather than tangential excision, and increase the number of surgical procedures required per patient. Twenty-four burned extremities were studied to measure blood loss, complications, and effectiveness of a technique for tangentially excising burns of extremities using tourniquet hemostasis followed by application of steel-wool-pad 'compression' dressings before tourniquet release. An average of 7.3 days postburn (PB), a mean of 7% body surface area (BSA) burn was excised per extremity with a mean blood loss of 29 ml/% BSA burn excised (less than one fifth of recently published values). Graft take averaged 91%. There was no evidence of neurocirculatory injury or other complications. When applied as described and carefully monitored, hemostatic tourniquets followed by 'compression' dressings can safely reduce blood loss associated with the exclision of limb burns and allow larger areas to be excised at each operation.

Total parenteral nutrition (TPN) is commonly used in the management of inflammatory bowel disease (IBD). Claims of its effectiveness are conflicting, and most reports have been limited to short-term assessments. We undertook a nonrandomized prospective study of the effects of TPN on the course of IBD in 30 patients whose disease was refractory to medical therapy, 20 with Crohn's disease and 10 with ulcerative colitis. Parameters of nutritional improvement, subjective and objective clinical response during TPN, and long-term outcome were assessed. All but one of the patients gained weight. Seven of the 20 Crohn's patients, including 3 of 4 with fistulas, had no response to TPN. The other 13 had reduction of diarrhea, relief of abdominal pain, and an improved sense of well-being during TPN. On long-term follow-up, five of these patients relapsed and required surgery; five remain improved with active disease controlled by medication 2--24 months later, and three are symptom-free and off all medication 20--48 months later. Clinical improvement during TPN was observed in only four of the 10 ulcerative colitis patients; six required colectomy after 9--24 days of TPN. Of the four responders, one relapsed and had colectomy one month later, two continue to have active disease controlled by medication five and 43 months later, and one has been symptom-free and off all medication for over three years. We conclude that TPN is useful adjunctive therapy for IBD patients requiring bowel rest and nutritional repletion. Dramatic clinical improvement occurs in some patients but is unpredictable.

The descending part of duodenum is the principal site for an intraluminally projecting mucosal pouch or diverticulum, but this unusual lesion may also occur elsewhere in the upper gastrointestinal tract. We report three patients in whom a large intraluminal duodenal diverticulum (IDD) was diagnosed radiographically at the ages of 15, 27, and 68 years, respectively. Fiberoptic duodenoscopy was performed in the two symptomatic cases for the removal of impacted food from IDD or dilatation of its outflow aperture. Guidelines for the diagnosis and treatment of IDD are provided based on our experience and review of the pertinent literature.

To determine the efficacy of azathioprine in the treatment of Crohn's disease, a 26-week double-blind trial was performed. 20 patients with Crohn's disease, requiring at least 10 mg of prednisone/day over the 3 months prior to entering the study were randomized into placebo (10 patients) and major criterion of success in the trial. There were 7 relapses in the placebo group (5 patients) and 2 relapses in the azathioprine group (2 patients). Complications including fistulae were not affected by the medications. The mean reduction in steriod dosage in the azathioprine group at the end of the trial (-15.5 mg) was greater than in the placebo group (-6.1 mg). These results suggest that azathioprine may permit reduction or discontinuation of steroids without the worsening of symptoms in some patients who appear to require steroids for control of their symptoms. The clinical features of this "AZA-responsive subgroup" remain to be defined.

In summary, the cooperative venture between the Office of Mental Health and the SUNY, Health Science Center has proved to be fruitful for both parties. It has achieved efficiency of volume by referral to one state-owned referral laboratory, yet has improved overall patient care.

The occurrence of inflammatory bowel disease in all three members of one family is described. Studies of white blood cell chromosomes, histocompatibility antigens, and cellular and humoral immunity failed to explain this unusual phenomenon. However, the appearance of inflammatory bowel disease in an entire family reemphasizes the potential role of genetic and environmental influences in the pathogenesis of some cases of ulcerative colitis and Crohn's disease.

Hypersensitivity reactions to cromolyn sodium occur rarely. On several occasions they have been associated with peripheral eosinophilia and granulomatous inflammation. Liver disease has not been reported previously as a complication of inhaled cromolyn. We describe here a woman in whom marked peripheral eosinophilia, liver disease, and systemic vasculitis developed while taking cromolyn and resolved or improved on discontinuation of the drug and treatment with corticosteroids. The liver disease was similar to primary biliary cirrhosis except that marked eosinophilic infiltration and granulomas were present initially. Studies of the patient's serum for binding of carbon 14-labeled cromolyn, the skin for deposits of the drug, and the circulating lymphocytes for stimulation by cromolyn failed to demonstrate any abnormalities. However, the elevated IgG and IgM levels, the positive rheumatoid factor and antimitochondrial antibody, and the reduced serum complement, which returned to normal on discontinuation of the drug therapy, suggests that immunologic mechanisms may have played a role in the pathogenesis of this patient's illness.

To determine the efficacy of azathioprine in the treatment of ulcerative colitis, a 6-month double blind trial was carried out. Thirty patients with chronic ulcerative colitis who required the equivalent of at least 10 mg of prednisone per day over the 3 months prior to entering the study were randomized into placebo and azathioprine (1.5 mg per kg) treatment groups. Reduction of steriods was a major objective of the trial. Age and sex distribution, number of bowel movements, sense of well being, steroid dosage, and findings on proctoscopy, rectal biopsy, and colon X-ray initially were similar in the two groups. No side effects were associated with azathioprine. Although steroid dose was lower (p less than 0.05) in the azathioprine group at the termination of the study, no difference between the two groups could be detected in the number of bowel movements, sense of well being, and findings on proctoscopy during the first 3 weeks compared with the last 3 and during the first 3 months compared with the last 3. Although azathioprine does not confer dramatic benefit upon patients with chronic ulcerative colitis who require steroids, it does permit reduction of steroid dosage without apparent worsening of the disease. Its major value in ulcerative colitis may be in facilitating significant decreases or complete discontinuance of steroids.

1. A continuously recording glass electrode apparatus has been described for measuring carbon dioxide concentration changes in solution. The limits of applicability of the apparatus have been analyzed. 2. The glass electrode apparatus has been used for the measurement of transient rates of photosynthesis by algal suspensions. 3. The decline of the photosynthetic rate in high light at carbon dioxide partial pressures less than 0.5 per cent atmosphere, observed in the glass electrode apparatus, has been confirmed by steady state experiments in which flowing gas streams were analyzed.

Three independent methods have been used to determine the size of the quantum accumulation unit in green plant photosynthesis. This unit is defined as that group of pigment molecules within which quantal absorption acts must take place leading to the evolution of a single O(2) molecule. All three methods take advantage of the nonlinearity of oxygen yield with light dose at very low dosages. The experimental values of this unit size, based on an assumed model for the charge cooperation in O(2) evolution, ranging from 800 to 1600, suggest that there is either limited energy transfer between energy-trapping units or chemical cooperation among oxygen precursors formed in several neighboring energy-trapping units. Widely diffusible essential precursors to molecular oxygen are ruled out by these results. Inhibition studies show that O(2) evolution is blocked when 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) is added to chloroplasts after two preliminary flashes and before a third flash which would have yielded O(2) in the absence of DCMU. This experiment is interpreted as evidence that the site of DCMU inhibition is on the oxidizing side of system II. Pretreatment of chloroplasts with large concentrations of Tris, previously believed to destroy O(2) evolution by blocking an essential reaction in the electron chain between water and system II, may be alternately interpreted as promoting the dark reversal of the system II light-induced electron transfer.

1. It has been shown that the glass electrode method as previously described by the author for measurements of transient rates in photosynthesis is free of systematic errors. 2. Justification has been given for the use of the steady state-gas flow method for measuring rates of assimilation under conditions in which the solution is known not to be seriously depleted of CO(2). 3. The decline of photosynthetic rates under light saturation at CO(2) pressures less than several tenths per cent of an atmosphere has been shown to be a real phenomenon. It has been suggested that there may be a real discrepancy between this finding and those of some other investigators due to a difference in the previous history of the algal suspensions.