Spontaneous evolution of modularity and network motifs

Biological networks have an inherent simplicity: they are modular with a design that can be separated into units that perform almost independently. Furthermore, they show reuse of recurring patterns termed network motifs. Little is known about the evolutionary origin of these properties. Current models of biological evolution typically produce networks that are highly nonmodular and lack understandable motifs. Here, we suggest a possible explanation for the origin of modularity and network motifs in biology. We use standard evolutionary algorithms to evolve networks. A key feature in this study is evolution under an environment (evolutionary goal) that changes in a modular fashion. That is, we repeatedly switch between several goals, each made of a different combination of subgoals. We find that such "modularly varying goals" lead to the spontaneous evolution of modular network structure and network motifs. The resulting networks rapidly evolve to satisfy each of the different goals. Such switching between related goals may represent biological evolution in a changing environment that requires different combinations of a set of basic biological functions. The present study may shed light on the evolutionary forces that promote structural simplicity in biological networks and offers ways to improve the evolutionary design of engineered systems.     

Recurrent rectal prolapse

PURPOSE: The aim of this study was to assess the clinical and functional outcome of surgery for recurrent rectal prolapse and compare it with the outcome of patients who underwent primary operation for rectal prolapse. METHODS: All patients who underwent surgery for rectal prolapse were evaluated for age, gender, procedure, anorectal manometry and electromyography findings, and morbidity. The results for patients who underwent surgery for recurrent rectal prolapse were compared with a group of patients matched for age, gender, surgeon, and procedure who underwent primary operations for rectal prolapse. RESULTS: A total of 115 patients underwent surgery for rectal prolapse. Twenty-seven patients, 10 initially operated on at this institution and 17 operated on elsewhere, underwent surgery for recurrent rectal prolapse. These 27 patients were compared with 27 patients with primary rectal prolapse operated on in our department. In the recurrent rectal prolapse group, prior surgery included rectopexy in 7 patients, Delorme's procedure in 7 patients, perineal rectosigmoidectomy in 7 patients, anal encirclement procedure in 4 patients, and resection rectopexy in 2 patients. Operations performed for recurrence were perineal rectosigmoidectomy in 14 patients, resection rectopexy in 8 patients, rectopexy in 2 patients, pelvic floor repair in 2 patients, and Delorme's procedure in 1 patient. There were no statistically significant differences between the groups in preoperative incontinence score (recurrent rectal prolapse, 13.6±7.8vs. rectal prolapse, 12.7±7.2; range, 0–20) or manometric or electromyography findings, and there were no significant differences in mortality (0vs. 3.7 percent), mean hospital stay (5.4±2.5vs. 6.9±2.8 days), anastomotic complications (anastomotic stricture (0vs. 7.4 percent), anastomotic leak (3.7vs. 3.7 percent) and wound infection (3.7vs. 0 percent)), postoperative incontinence score (2.8±4.8vs. 1.5±2.7), or recurrence rate (14.8vs. 11.1 percent) between the two groups at a mean follow-up of 23.9 (range, 6–68) and 22 (range, 5–55) months, respectively. The overall success rate for recurrent rectal prolapse was 85.2 percent. CONCLUSION: The outcome of surgery for rectal prolapse is similar in cases of primary or recurrent prolapse. The same surgical options are valid in both scenarios.Funded in part by a generous grant from the Eleanor Naylor Dana Charitable Trust Fund and the Caporella Family.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, Philadelphia, Pennsylvania, June 22 to 26, 1997.     

A holistic approach to chronic pain management that involves all stakeholders: change is needed

Chronic pain affects a large proportion of the population, imposing significant individual distress and a considerable burden on society, yet treatment is not always instituted and/or adequate. Comprehensive multidisciplinary management based on the biopsychosocial model of pain has been shown to be clinically effective and cost-efficient, but is not widely available. A literature review of stakeholder groups revealed many reasons for this, including: i) many patients believe healthcare professionals lack relevant knowledge, and consultations are rushed, ii) general practitioners consider that pain management has a low priority and is under-resourced, iii) pain specialists cite non-adherence to evidence-based treatment, sub-optimal prescribing, and chronic pain not being regarded as a disease in its own right, iv) nurses’, pharmacists’ and physiotherapists’ skills are not fully utilized, and v) psychological therapy is employed infrequently and often too late.

Many of the issues relating to physicians could be addressed by improving medical training, both at undergraduate and postgraduate levels – for example, by making pain medicine a compulsory core subject of the undergraduate medical curriculum. This would improve physician/patient communication, increase the use of standardized pain assessment tools, and allow more patients to participate in treatment decisions. Patient care would also benefit from improved training for other multidisciplinary team members; for example, nurses could provide counseling and follow-up support, psychologists offer coping skills training, and physiotherapists have a greater role in rehabilitation. Equally important measures include the widespread adoption of a patient-centered approach, chronic pain being recognized as a disease in its own right, and the development of universal guidelines for managing chronic non-cancer pain.

Perhaps the greatest barrier to improvement is lack of political will at both national and international level. Some powerful initiatives and collaborations are currently lobbying policy-making bodies to raise standards and reduce unnecessary pain – it is vital they continue.     

Hypertension in a Brazilian Urban Slum Population

Low- and middle-income countries account for the majority of hypertension disease burden. However, little is known about the distribution of this illness within subpopulations of these countries, particularly among those who live in urban informal settlements. A cross-sectional hypertension survey was conducted in 2003 among 5649 adult residents of a slum settlement in the city of Salvador, Brazil. Hypertension was defined as either an elevated arterial systolic (≥140 mmHg) or diastolic (≥90 mmHg) blood pressure. Sex-specific multivariable models of systolic blood pressure were constructed to identify factors associated with elevated blood pressure. The prevalence of hypertension in the population 18 years and older was 21 % (1162/5649). Men had 1.2 times the risk of hypertension compared with women (95 % confidence intervals (CI), 1.05, 1.36). Increasing age and lack of any schooling, particularly for women, were also significantly associated with elevated blood pressure (p < 0.05). There was also a direct association between men who were black and an elevated blood pressure. Among those who were hypertensive, 65.5 % were aware of their condition, and only 36.3 % of those aware were actively using anti-hypertensive medications. Men were less likely to be aware of their diagnosis or to use medications (p < 0.01 for both) than women. The prevalence of hypertension in this slum community was lower than reported frequencies in the non-slum population of Brazil and Salvador, yet both disease awareness and treatment frequency were low. Further research on hypertension and other chronic non-communicable diseases in slum populations is urgently needed to guide prevention and treatment efforts in this growing population.     

Quality of primary health care in China: an analysis of data from a nationwide longitudinal survey

Background

China has made remarkable efforts and achievements since its health reform in 2009, yet there are substantial knowledge gaps in the quality of primary health care (PHC) in China. We aimed to assess the quality of PHC in China by analysing hospital admission rates among diabetics, a frequently used quality indicator for PHC.

Diagnostic assessment of recurrent unexplained syncope with a new subcutaneously implantable loop recorder. Reveal-Investigators.

AIM: Patients with recurrent syncope undiagnosed after extensive non-invasive and invasive testing pose a diagnostic and therapeutic dilemma. Holter monitoring is nondiagnostic in 90% of cases. Recent developments in loop recorder technology permit long-term ECG monitoring in patients with recurrent unexplained syncope. The aim of this study was to report the worldwide experience with a new subcutaneously implantable loop recorder, implanted in 133 patients with unexplained syncope and negative laboratory investigations. METHODS AND RESULTS: The implantable loop recorder monitors continuously a single lead electrogram using two sensing electrodes on the device shell. The device was implanted in 133 patients, 67 male and 66 female with recurrent syncope. During a mean follow-up of 10.8 +/- 4.3 months after device implantation, 83 patients (62%) experienced syncope or pre-syncope. In the remaining 50 patients no diagnosis could be made because either no events occurred, the patients were lost to follow-up, had adverse events, or died prior to diagnosis. In 72 of the 83 patients with syncope during follow-up (87%), loop recording definitively determined whether an arrhythmia was the cause of symptoms or not. Diagnosis included bradycardia in 21 patients, pacemaker dysfunction in one patient, and tachycardia in 10 patients. One patient experienced multiple rhythm disturbances. Syncope was non-arrhythmic in 40 patients. The remaining 11 patients failed to press the activator. Therapy was instituted in all patients, in whom an arrhythmic cause was found. Severe anticipated device related complications occurred in three patients. CONCLUSION: An implantable loop recorder is useful for establishing a diagnosis when symptoms are recurrent but too infrequent for conventional monitoring techniques.     

Diastolic blood pressure is the first to rise in association with early subclinical obstructive sleep apnea: lessons from periodic examination screening

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is associated with long-term cardiovascular morbidity. Little is known about these relations at early stages. We conducted a case-control study in which we analyzed the clinical characteristics of young adults who underwent a periodic health examination and were screened for, and eventually found to experience, OSAS. METHODS: We identified 121 subjects newly diagnosed in a sleep study as having OSAS, and 229 matched control subjects in which screening for OSAS was negative. All had a medical interview, physical examination, and routine laboratory tests. RESULTS: Subjects who had OSAS had a higher, body mass index (3-kg/m(2) difference) and a higher diastolic blood pressure (4-mm Hg difference) value, without elevation in systolic blood pressure. There was no metabolic difference (lipids profile and fasting glucose levels) between groups. CONCLUSIONS: Diastolic blood pressure is higher early in the course of OSAS. Long term follow-up may determine effects of prevention and early intervention in OSAS and associated hypertension.     

Human fetal and cord serum thyroid hormones: developmental trends and interrelationships

Thyroid hormone is essential for fetal and neonatal development in particular of the brain, but little is known about regulation of fetal thyroid hormone levels throughout human gestation. The purpose of this study was to clarify developmental trends and interrelationships among T(4), free T(4) (FT4), thyroxine-binding globulin (TBG), TSH, T(3), rT(3), and T(4) sulfate (T4S) levels in cord and fetal blood sera (n = 639, 15-42 wk gestation) and correlate infant levels (23-42 wk gestation) to maternal values (n = 428, 16-45 yr) and those of nonpregnant women (n = 233, 16-46 yr). In cord and fetal serum, T(4), T(3), and TBG levels increase with gestation until term; TSH, FT4, T4S, and rT(3) levels increase and peak in the late second/early third trimester and then decline to term; T(4)/TBG ratios increase until late second trimester and plateau to term. Term cord sera TSH, TBG, and all iodothyronine levels, except T(3), are higher than nonpregnant women. In the third trimester, cord serum FT4, TSH, rT(3), and T4S levels are also higher than corresponding maternal levels, but T(4), T(3), and TBG levels are lower than maternal values. The late second/early third trimester is a critical transition period in fetal thyroid hormone metabolism, which may be interrupted by preterm birth and contribute to postnatal thyroid dysfunction.     

Acquired factor VII deficiency in hematopoietic stem cell transplant recipients

Acquired factor VII (FVII) deficiency in the absence of vitamin K deficiency, oral anticoagulant therapy, synthetic liver dysfunction, or DIC is rare, with only a handful of cases thus far reported. In the period from 1990 to 1996 we identified eight patients with acquired FVII deficiency, all of whom presented with prolongation of the prothrombin time (PT) in the first 2 weeks following stem cell transplantation (SCT). The mean plasma FVII clotting activity (FVII:c) was 22% (range 8-35%) with an approximately equivalent reduction in FVII antigen (FVII:Ag) level. Mean plasma levels of fibrinogen and factors II, V, IX, and X were normal. Protein C activity was significantly depressed in only one of the three patients in whom it was measured. Several patients experienced bleeding complications, and hemorrhage directly accounted for death in two cases. Veno-occlusive disease of the liver developed in three patients. We conclude that FVII deficiency should be considered in the differential diagnosis of prolonged PT in patients who have recently undergone SCT. The mechanism of this acquired deficiency state remains to be defined.