Neuropsychological examination detects post-operative complications in idiopathic normal pressure hydrocephalus (iNPH): report of two cases

Subdural fluid collections (SFC) are characteristic complications of shunting for idiopathic normal pressure hydrocephalus (iNPH). This report presents two shunted iNPH patients with clinically silent postoperative SFC, detected after abnormal neuropsychological findings. These cases highlight the value of neuropsychological assessment in the routine postoperative assessment of iNPH.     

Variations in the Use of Diagnostic Criteria for Developmental Dysplasia of the Hip

Background

Wide variation exists in reported prevalence estimates and management standards of developmental dysplasia of the hip (DDH). Discrepancies in diagnosticians’ opinions may explain some of this variation.

Questions/purposes

We sought to determine (1) the consistency with which pediatric orthopaedic surgeons rate the importance of diagnostic criteria for DDH, and (2) whether there were geographic differences in how the diagnostic criteria were rated by surgeons.

Methods

One hundred ninety-seven of 220 members of the European Paediatric Orthopaedic Society and 100 of 148 members of the British Society of Children’s Orthopaedic Surgery treating children with DDH participated in this cross-sectional study across 35 countries (15 regions). Each rated 37 items in four domains that specialists previously had identified as the most important features associated with DDH in early infancy. We determined consistency using the intraclass correlation coefficient (ICC; two-way random-effects model) interpreted as poor (0–0.40), acceptable (0.41–0.74), or good (≥ 0.75).

Results

Poor consistency among surgeons was found in rating the 37 diagnostic criteria (ICC, 0.33; 95% CI, 0.24–0.45). Consistency was poor for three domains (patient characteristics/history: ICC, 0.29; 95% CI, 0.16–0.58; ultrasound: ICC, 0.26; 95% CI, 0.14–0.52; radiography: ICC, 0.34; 95% CI, 0.12–0.95) and acceptable for one (clinical examination: ICC, 0.50; 95% CI, 0.33–0.73). Surgeons in particular regions appeared to have a concept of DDH diagnosis that distinguished them from specialists of other regions; consistency in eight regions was greater (ICC ≥ 0.40) than consistency among all 15 regions.

Conclusions

The consistency of specialists in rating diagnostic criteria for DDH was lower than expected, and there was considerable geographic variation in terms of how specialists assigned importance ratings of the diagnostic criteria; these findings are somewhat counterintuitive, given the frequency with which this condition is diagnosed. These inconsistencies could explain, partly, the widely differing prevalence estimates and management standards of DDH.     

The role of adipocytokines in insulin resistance in normal pregnancy: visfatin concentrations in early pregnancy predict insulin sensitivity

BACKGROUND: Throughout pregnancy maternal adipose tissue is metabolically active, producing adipocytokines involved in the process of insulin resistance. We explored the role of serum adipocytokines, including the newly identified adipocytokine visfatin, in the process of insulin resistance in normal pregnancy. METHODS: We examined 80 pregnant nonobese, nondiabetic white women during the 3 trimesters of pregnancy. All study participants underwent anthropometric measurements, adipocytokine evaluation, and a 75-g oral glucose tolerance test. Homeostasis mathematical model assessment (HOMA-R), insulin sensitivity index (ISI), and indices of beta-cell secretion were calculated. RESULTS: Maternal weight, percentage total body fat, hip circumference, and indices of beta-cell secretion increased significantly during the 3 trimesters, and HOMA-R and ISI increased and decreased, respectively, in the 3rd trimester. During early pregnancy, insulin resistance, beta-cell secretion, and weight correlated positively with leptin. During the 1st trimester, visfatin correlated negatively with percentage body fat and was the best positive predictor of 2nd trimester ISI. In the 2nd trimester, serum visfatin was the best negative predictor of percentage body fat. CONCLUSIONS: During normal pregnancy of nonobese, nondiabetic women, adipose tissue increases, accompanied by a significant progressive increase of insulin resistance. Visfatin concentrations in the 1st trimester positively predict insulin sensitivity during the 2nd trimester. Body fat mass during 1st trimester of pregnancy is negatively associated with insulin sensitivity during the 2nd trimester and perhaps should be kept under control.     

A large presacral tailgut cyst with a carcinoid tumor in a male: report of a case

Tailgut cysts are developmental hamartomas found in the presacral space. They are usually detected incidentally during physical examinations or imaging studies. However, they may cause symptoms due to compression of nearby organs. Due to their potential malignant transformation, surgical resection is warranted, while routine biopsy is considered controversial because of the concern about infection of the tailgut cyst and needle-track implantation of malignant cells. The co-existence of a carcinoid in a tailgut cyst is extremely rare. Only 16 cases have been reported previously, the vast majority of which were found in females. We herein present the case of a carcinoid in a tailgut cyst found in a male patient, discuss the potential pathogenesis of tailgut carcinoids, and underline the fact that their previous consideration of the condition as a female-restricted entity should be rejected.     

Threonine-17 phosphorylation of phospholamban: a key determinant of frequency-dependent increase of cardiac contractility

Multiple studies have shown that phospholamban (PLN) plays a key role in regulation of frequency-dependent increase of cardiac contraction, a hallmark of the contractile reserve in myocardium. However, the mechanisms underlying this relationship remain elusive. Phosphorylation of PLN occurs on residues: serine-16 (Ser(16)) and threonine-17 (Thr(17)) in vivo. In isolated wild-type cardiomyocytes, we found that increases of stimulation frequency from 0.5 to 5 Hz were associated with increased Thr(17) phosphorylation of PLN and cardiac contractility. To further delineate the role of PLN phosphorylation in the frequency-dependent increases of cardiac function, three transgenic mouse models, expressing wild-type, Ser16Ala (S16A), or Thr17Ala (T17A) mutant PLN in the null background were generated. Transgenic lines expressing similar levels of wild-type or mutant PLN were selected and isolated cardiomyocytes were paced from 0.5 to 5 Hz. Upon increases in pacing frequency, the fractional shortening (FS) and rates of contraction (+dL/dt) and relaxation (-dL/dt) increased in wild-type and S16A mutant PLN cardiomyocytes. In contrast, in myocytes expressing the T17A mutant PLN, there were no increases in FS and +/-dL/dt upon increasing the frequency of stimulation. The time to 50% peak shortening (TTP(50)) and to 50% relaxation (TTR(50)) were also abbreviated to a much higher extent (two-fold) in wild-type and S16A mutant compared to T17A mutant PLN cardiomyocytes. These results indicate that Thr(17) phosphorylation of PLN is the major contributor to frequency-dependent increases of contractile and relaxation parameters in mouse cardiomyocytes, although some increases in these parameters occur even in the absence of PLN phosphorylation. Thus, the positive force-frequency relationship in cardiomyocytes is mechanistically and mainly related to PLN phosphorylation.     

Structural plasticity of 4-α-helical bundles exemplified by the puzzle-like molecular assembly of the Rop protein

The dimeric Repressor of Primer (Rop) protein, a widely used model system for the study of coiled-coil 4-α-helical bundles, is characterized by a remarkable structural plasticity. Loop region mutations lead to a wide range of topologies, folding states, and altered physicochemical properties. A protein-folding study of Rop and several loop variants has identified specific residues and sequences that are linked to the observed structural plasticity. Apart from the native state, native-like and molten-globule states have been identified; these states are sensitive to reducing agents due to the formation of nonnative disulfide bridges. Pro residues in the loop are critical for the establishment of new topologies and molten globule states; their effects, however, can be in part compensated by Gly residues. The extreme plasticity in the assembly of 4-α-helical bundles reflects the capacity of the Rop sequence to combine a specific set of hydrophobic residues into strikingly different hydrophobic cores. These cores include highly hydrated ones that are consistent with the formation of interchain, nonnative disulfide bridges and the establishment of molten globules. Potential applications of this structural plasticity are among others in the engineering of bio-inspired materials.Recurrent motifs of tertiary structure are convenient model systems for studying protein folding and potentially also for the design of bio-inspired materials. For protein design purposes, structural plasticity is an important, although poorly understood, parameter to be considered, as it is among the main reasons that the re-engineering of proteins toward novel materials is not yet satisfactorily manageable (1, 2).The present study focuses on the structural plasticity associated with the 4-α-helical bundle (4HB) motif. 4HBs consist of four amphipathic α-helices packed in a parallel or antiparallel fashion (3, 4). Their folding is largely determined by a repeating pattern of hydrophobic and hydrophilic residues, organized on the basis of seven-residue repeats (heptads) (5). Being the simplest tertiary motif, 4HBs have been subject to numerous protein-folding studies; attempts have been made to exploit them as building blocks for bio-inspired materials (6).A paradigm of a highly regular 4HB is the RNA-binding ColE1 Repressor of Primer (Rop) protein (7–9), also referred to as RNA-one-modulator (ROM). Each monomer is an α-helical hairpin consisting of two antiparallel α-helices connected by a short loop. The sequence of Rop displays a heptad repeats pattern that is interrupted only in the loop region.Structural simplicity makes Rop an attractive model system for the study of the folding of 4HBs. The loop region and the hydrophobic core have thereby attracted particular attention, as these regions are linked with the remarkable ability of Rop mutants to adopt altered topologies and properties (10–15). Striking examples of loop variants include mutant Loopless Rop (LLR), in which an uninterrupted pattern of heptad repeats is established through a five-residue deletion in the loop. In this “loopless” mutant, the α-helical hairpin of the monomer is converted into a single helix (15, 16). The complete LLR molecule is a tetramer that is completely reorganized relative to the dimeric wild-type (WT) Rop, thereby becoming a hyper-thermostable protein (16). On the other hand, establishment of an uninterrupted heptad periodicity through a two-residue insertion in the loop produces minimal changes relative to WT in terms of structure and properties (12). Thus, these two mutants with uninterrupted patterns of heptads reveal that there is a considerable structural plasticity inherent to the Rop sequence, but the relationship between heptad periodicity and the structural/physicochemical properties is complex.Extreme structural plasticity producing completely altered 4HB topologies is also associated with point mutations in the loop region. Replacement of loop residue Ala31 by Pro (17) results in a complete reorganization of the entire protein, which is converted from the canonical left-handed, all-antiparallel form into a right-handed mixed-parallel and antiparallel 4-α-helical bundle, displaying a “bisecting U” topology that is to a large extent determined by the local conformation at residue 31 (18). Mutant A31P displays two variations of the bisecting U topology; these differ in the relative juxtaposition of the α-helices (19). These conformations crystallize in different space groups (orthorhombic and monoclinic); both space groups have been occasionally observed in the same crystallization drop, indicating the coexistence of the two forms in solution. Molecular dynamics simulations for A31P have demonstrated a potential for the interconversion between the two conformations (14).Hydrophobic core mutants occasionally also display structural plasticity producing a new (“syn”) topology (20) that results from the “anti”-topology of WT through a 180° flip of one monomer around the dyad axis normal to the long axis of WT. The competition between the anti and syn topologies and the mixture of the two structures have been studied in detail for some Rop mutants (21, 22).Apart from structural plasticity, a closely related issue associated with the folding of Rop is the role of Cys residues (Cys-38 and Cys-52). Both residues are buried in the hydrophobic core and are not involved in the formation of disulfide bridges in any of the known structures of WT and its mutants. Surprisingly, however, a Cys-free variant (CYSfree) that conserves the structure, stability, and in vivo activity of WT exhibits dramatically faster unfolding kinetics (23).The present study focuses on the role of the loop region and Cys residues in the structural plasticity of Rop. To explore the conversion of the WT anti-topology into the bisecting U topology of A31P, the three double mutants D30P/A31G (PG), D30G/A31P (GP), and D30P/A31P (PP) have been constructed for loop positions 30 and 31. These mutations combine the effects of the most constrained amino acid (Pro) and of the least constrained one (Gly). In addition, the potential role of Cys residues in Rop folding is explored by following the effects of reducing agents.     

Sleep Deprivation: Effects on Weight Loss and Weight Loss Maintenance

This narrative review presents the findings from intervention studies on the effects of sleep deprivation on eating habits, metabolic rate, and the hormones regulating metabolism, and discusses their relevance to weight loss efforts. Disturbed sleeping patterns lead to increased energy intake, partly from excessive snacking, mainly on foods high in fat and carbohydrates. The studies focused mainly on the effects of sleep duration, but also of sleep quality, on dietary intake during weight loss trials, and on weight loss maintenance. It is important to explore sleep routines that could enhance the efforts of obese and overweight people to lose weight, maintain their weight loss, and improve their overall health.