Primary Sjögren's syndrome as a systemic disease: a study of participants enrolled in an international Sjögren's syndrome registry

Objective

To study the prevalence of extraglandular manifestations in primary Sjögren's syndrome (SS) among participants enrolled in the Sjögren's International Collaborative Clinical Alliance (SICCA) Registry.

Methods

A total of 1,927 participants in the SICCA registry were studied, including 886 participants who met the 2002 American–European Consensus Group (AECG) criteria for primary SS, 830 “intermediate” cases who had some objective findings of primary SS but did not meet AECG criteria, and 211 control individuals. We studied the prevalence of immunologic and hematologic laboratory abnormalities, specific rheumatologic examination findings, and physician‐confirmed thyroid, liver, and kidney disease, as well as lymphoma among SICCA participants.

Results

Laboratory abnormalities, including hematologic abnormalities, hypergammaglobulinemia, and hypocomplementemia, frequently occurred among primary SS cases and were more common among the intermediate cases than among control participants. Cutaneous vasculitis and lymphadenopathy were also more common among primary SS cases. In contrast, the frequency of physician‐confirmed diagnoses of thyroid, liver, and kidney disease and lymphoma was low and only primary biliary cirrhosis was associated with primary SS case status. Rheumatologic and neurologic symptoms were common among all SICCA participants, regardless of case status.

Conclusion

Data from the international SICCA registry support the systemic nature of primary SS, manifested primarily in terms of specific immunologic and hematologic abnormalities. The occurrence of other systemic disorders among this cohort is relatively uncommon. Previously reported associations may be more specific to select patient subgroups, such as those referred for evaluation of certain neurologic, rheumatologic, or other systemic manifestations.     

Omentectomy added to Roux-en-Y gastric bypass surgery: a randomized,controlled trial

BackgroundExcess visceral adipose tissue predicts for incipient diabetes mellitus and cardiovascular disease. Human data are mixed regarding the benefits of selective visceral adipose tissue reduction. We investigated the effects of omentectomy added to laparoscopic Roux-en-Y gastric bypass on glucose homeostasis and lipids, inflammatory markers, and adipokines 90 days postoperatively in nondiabetic patients at the Legacy Good Samaritan Hospital and Oregon Health and Science University (Portland, OR).MethodsA single-blind, randomized study of laparoscopic Roux-en-Y gastric bypass plus omentectomy versus laparoscopic Roux-en-Y gastric bypass alone in 28 subjects (7 men and 21 women). The groups were matched at baseline for gender, age, and body mass index (BMI). The eligibility criteria included age ≥18 years, BMI ≥40 and <50 kg/m² without co-morbid conditions or BMI ≥35 and <50 kg/m² with co-morbid conditions. The primary outcome measures were changes in the fasting plasma glucose, insulin, and homostatic model assessment of insulin resistance. The secondary measures were BMI and the high-sensitivity C-reactive protein, tumor necrosis factor-α, interleukin, total and high-molecular-weight adiponectin, fibrinogen, and plasminogen activator inhibitor-1 levels.ResultsAfter surgery, the BMI decreased significantly in both groups and was not different at the follow-up point. Although many outcome parameters improved with weight loss in both groups postoperatively, only the omentectomy group experienced statistically significant decreases in fasting glucose (P < .05), total (P = .004) and very-low-density lipoprotein (P = .001) cholesterol, and an increase in the high-molecular-weight/total adiponectin ratio (P = .013).ConclusionsOmentectomy added to laparoscopic Roux-en-Y gastric bypass results in favorable changes in glucose homeostasis, lipid levels, and adipokine profile at 90 days postoperatively. These data support the hypothesis that selective ablation of visceral adipose tissue conveys metabolic benefits in nondiabetic humans.     

Estrogen and muscle stiffness have a negative relationship in females

Purpose  

Hormonal fluctuations are one potential reason why females might have a greater rate of noncontact ACL injury. The hamstrings are capable of limiting anterior cruciate ligament (ACL) loading. This study examined whether relationships existed between reproductive hormones (estradiol-β-17, free testosterone, and progesterone) and hamstring neuromechanical variables (hamstring musculotendinous stiffness (MTS), rate of force production (RFP), time to 50% peak torque (T50%), and electromechanical delay (EMD)) in genders combined and independently.     

Compartmentalization of the protein repair machinery in photosynthetic membranes

A crucial component of protein homeostasis in cells is the repair of damaged proteins. The repair of oxygen-evolving photosystem II (PS II) supercomplexes in plant chloroplasts is a prime example of a very efficient repair process that evolved in response to the high vulnerability of PS II to photooxidative damage, exacerbated by high-light (HL) stress. Significant progress in recent years has unraveled individual components and steps that constitute the PS II repair machinery, which is embedded in the thylakoid membrane system inside chloroplasts. However, an open question is how a certain order of these repair steps is established and how unwanted back-reactions that jeopardize the repair efficiency are avoided. Here, we report that spatial separation of key enzymes involved in PS II repair is realized by subcompartmentalization of the thylakoid membrane, accomplished by the formation of stacked grana membranes. The spatial segregation of kinases, phosphatases, proteases, and ribosomes ensures a certain order of events with minimal mutual interference. The margins of the grana turn out to be the site of protein degradation, well separated from active PS II in grana core and de novo protein synthesis in unstacked stroma lamellae. Furthermore, HL induces a partial conversion of stacked grana core to grana margin, which leads to a controlled access of proteases to PS II. Our study suggests that the origin of grana in evolution ensures high repair efficiency, which is essential for PS II homeostasis.Repair of damaged protein complexes is essential for the survival of all living organisms. One of nature’s most efficient repair machineries is localized in photosynthetic thylakoid membranes of plants, which can turn over the total pool of the water-splitting photosystem II (PS II) supercomplex in less than 1 h (1). This remarkable potential for protein repair is crucial for the survival and fitness of plants because photodamage by reactive oxygen species is an inherent feature of PS II photochemistry. Significant knowledge gained over the past decade identifies individual steps involved in PS II repair. This progress has led to the formulation of a repair cycle that describes the life cycle of PS II, proceeding from its damage, disassembly, degradation, and resynthesis to its reassembly (2–4).To appreciate the challenges for repairing damaged PS II, it is essential to understand two structural features of the thylakoid membrane system. The first is that functional PS II is organized as a dimeric 1.4-MDa supercomplex in which each monomer consists of at least 28 subunits with two trimeric light harvesting complexes II (LHC II) attached to the core (5, 6). Within this huge supercomplex, the main target of photodamage is the central D1 subunit (7). The PS II repair cycle is therefore mainly designed for specific replacement of the damaged D1, which requires disassembly and reassembly of the whole supercomplex. The second characteristic is that in plants, some of thylakoid membranes pile up to strictly stacked cylindrical grana membranes (8, 9). The consequence of grana formation is four distinct domains: The flat, strictly stacked grana core membranes are connected to unstacked stroma lamellae via highly curved grana margins that are located at the periphery of the grana cylinder. The grana cylinder is sealed at the top and bottom by the flat so-called “end membranes.” Recently, a curvature thylakoid (CURT) protein family has been identified that facilitates the physical bending of grana margins (10). Consequently, CURT proteins are highly enriched in grana margins (10). These structural boundary conditions realized in thylakoid membranes have important consequences for the PS II repair cycle. The damage to the supercomplex occurs in stacked grana, where most of PS II is concentrated. The replacement of damaged D1, however, takes place in stroma lamellae. Thus, PS II repair depends on brisk protein trafficking between grana core, margins, and stroma lamellae, which is challenged by very low PS II mobility in grana core membranes caused by the macromolecular crowding (11).The mainstream model for the order of events of the PS II repair cycle starts with the phosphorylation of PS II core subunits (D1, D2, CP43, and PsbH) in the supercomplex, catalyzed mainly by the protein kinase Stn8 (12). PS II core phosphorylation triggers disassembly of the supercomplex (13, 14), which is required for mobilization of PS II from the rather immobile protein matrix in grana core (15). After migration of the trimmed down PS II complex to the unstacked thylakoid regions, it is dephosphorylated by the PS II core phosphatase (PBCP) (16) and by other putative PS II phosphatases. This dephosphorylation step is followed by the degradation of the damaged D1 by FtsH and Deg proteases. A new D1 subunit, which is de novo synthesized at the plastidial 70S ribosomes and processed by the CtpA peptidase, is inserted into the truncated PS II complex. The PS II repair cycle is completed by the reassembly of the supercomplex and its back-migration to grana core. The role of PS II core phosphorylation has been controversial. However, there is now consensus that it is required for ultrastructural changes of the thylakoid membrane system and for the mobilization of PS II in grana core (13, 14, 17).A crucial open question in the PS II repair cycle is how the specific order of events is established and controlled. The significance of this question is demonstrated by the fact that some steps are reverse reactions of the preceding steps (e.g., dephosphorylation follows phosphorylation, D1 synthesis follows D1 degradation). Uncontrolled intermixing of these reactions could lower the efficiency of the whole repair process. As for all multistep metabolic pathways, coordination and fine-tuning of the individual steps are required for the PS II repair cycle. In this study, we show that confining enzymes involved in PS II repair to distinct subcompartments in thylakoid membranes is a strategy to avoid uncontrolled back-reactions. We identify that the different thylakoid membrane subcompartments have distinct roles in the PS II repair cycle. In particular, the grana margins play a pivotal role.