Bone “mass” and the “mechanostat”: A proposal

The observed fit of bone mass to a healthy animal's typical mechanical usage indicates some mechanism or mechanisms monitor that usage and control the three longitudinal growth, bone modeling, and BMU-based remodeling activities that directly determine bone mass. That mechanism could be named a mechanostat. Accumulated evidence suggests it includes the bone itself, plus mechanisms that transform its mechanical usage into appropriate signals, plus other mechanisms that detect those signals and then direct the above three biologic activities. In vivo studies have shown that bone strains in or above the 1500–3000 microstrain range cause bone modelling to increase cortical bone mass, while strains below the 100–300 microstrain range release BMU-based remodeling which then removes existing cortical-endosteal and trabecular bone. That arrangement provides a dual system in which bone modeling would adapt bone mass to gross overloading, while BMU-based remodeling would adapt bone mass to gross underloading, and the above strain ranges would be the approximate “setpoints” of those responses. The anatomical distribution of those mechanical usage effects are well known. If circulating agents or disease changed the effective setpoints of those responses their bone mass effects should copy the anatomical distribution of the mechanical usage effects. That seems to be the case for many agents and diseases, and several examples are discussed, including postmenopausal osteoporosis, fluoride effects, bone loss in orbit, and osteogenesis imperfecta. The mechanostat proposal is a seminal idea which fits diverse evidence but it requires critique and experimental study.     

Polymers by 1,3-dipolar cycloaddition reactions: the “criss-cross” cycloaddition

1,3-Dipolar cycloaddition reactions have been used to prepare a large number of different heterocyclic and heteroaromatic polymers. Most of this work has been done in the 60's and 70's. Since then, interest in this field has vanished almost completely. While the number of polymer structures accessible by 1,3-dipolar cycloaddition is very large, the high reactivity and tendency of the 1,3-dipoles to undergo side reactions limits the successful applications in step growth polymer synthesis considerably. The “criss-cross” cycloaddition reaction also proceeds via two consecutive 1,3-dipolar cycloaddition steps. Its starting compounds, azines and diolefins or diisocyanates, are stable, can be purified easily, and do not undergo side reactions if the reaction conditions are chosen properly. Initially, the reaction between hexafluoroacetone azine and various diolefins was studied. This work was aimed at the preparation and structural characterization of soluble polymers. Later on, the “criss-cross” cycloaddition between aromatic aldazines and diisocyanates was included in this research. Different azines and diisocyanates were studied to find the best compromise between reactivity of the monomers and solubility and glass transition temperature of the products. Due to the special reaction mechanism, the polymers have exclusively isocyanate end groups, independent of stoichiometry of the monomers and the conversion. Thus, this reaction is ideally suited for the preparation of telechelics. Prepolymers obtained by “criss-cross” cycloaddition between 4-methoxybenzaldazine and 4,4′-diisocyanatodiphenyl ether were used as hard segments in segmented block copolymers. Those block copolymers with a hard segment content below 36% showed elastomeric behavior with ultimate elongations above 700% and tensile strengths between 2 and 6 MPa.     

“Heavy‐Atom” Donor–Acceptor Conjugated Polymers

Heavy‐atom substitution chemistry in donor–acceptor (D–A) conjugated polymers has gained increasing attention in the past few years. Overall, the introduction of “heavy” atoms (below C in group 14; below N in group 15; below S in group 16) into D–A conjugated polymers allows control over properties through relatively straightforward synthetic chemistry, and produces materials with high molecular weights (>20 000 g mol^?1), strong absorption (ε ≈ 40 000 L mol^?1 cm^?1), narrow highest occupied molecular orbital (HOMO)–lowest unoccupied molecular orbital (LUMO) gaps (<1 eV), as well as high charge‐carrier mobility (>10^?2 cm² V^?1 s^?1). This Trend article aims to describe heavy‐atom substitution effects in D–A polymers, and their applications, by systematically examining representative polymer structures.

     

Psychiatric “Co-occurrence”? I'll Stick with “Comorbidlty”

Lilienfeld et al's critique of the use of the term comorbid in psychopathological research is critically examined. They are incorrect in asserting that the original use of the term in medical epidemiology was intended to restrict it to disease entities. Furthermore, the ways in which medical comorbidity can be understood apply equally well to understanding the comorbidity of psychiatric or psychological disorders. Just as it has been useful to use the general term psychiatric disorders to include symptom patterns and syndromes and few If any true diseases, so to it is useful to apply the generic term of comorbidity to the joint occurrence of psychiatric disorders. Because methodological factors can sometimes contribute to artifactual comorbidity which is uninformative about the disorders being studied is no reason to abandon the term comorbidity in psycho-pathological research.     

Smith-Lemli-Opitz syndrome: Thirty-year follow-up of “S” of “RSH” syndrome

We have reassessed patient “S,” one of the first 3 individuals recognized to have Smith-Lemli-Opitz (or RSH) syndrome, at age 34 years, and we describe his physical, developmental, and behavioral manifestations. This reassessment provides formal evidence that this individual has the cholesterol biosynthetic defect which is thought to be the cause of Smith-Lemli-Opitz syndrome. Dietary manipulation appears to have had a beneficial effect on the patient's behavior and suggests that even in adults with this condition, dietary cholesterol supplementation may be indicated. Am. J. Med. Genet. 68:260–262, 1997. © 1997 Wiley-Liss, Inc.     

Polymers by “criss-cross”-cycloaddition, 7. Segmented block copolymers

“Criss-cross”-cycloaddition of 4,4′-diisocyanatodiphenyl ether and 4-methoxybenzaldazine was used to synthesize α,ω-diisocyanato telechelics of molecular weights between 1 600 and 3 900. These precursors were reacted with different α,ω-dihydroxy functionalized aliphatic polyethers to produce segmented block copolymers in which the precursors obtained by cycloaddition reaction provide hard segment domains embedded in a polyether soft segment matrix. The resulting materials were soluble in common organic solvents such as tetrahydrofuran and chloroform and were characterized by spectroscopic techniques (¹H-, ¹³C NMR, IR spectroscopy) as well as gel permeation chromatography (GPC) for molar mass determination. The block copolymers were molded in a hot stage press, and the resulting samples were characterized by differential scanning calorimetry (DSC), dynamic mechanical thermal analysis (DMTA) and stress-strain measurement. The materials with a hard segment fraction below 0.36 and a molecular weight above M?_n = 90 000 were elastomers with ultimate elongations above 700%.     

Endocardial cushion defect: Further studies of “isolated” versus “syndromic” occurrence

The isolated occurrence of endocardial cushion defect (ECD) has been suggested to differ from its occurrence within the context of a syndrome, with regard to the nature (complete or partial) of the defect and the associated cardiovascular malformations. Analysis of data derived from the Baltimore-Washington Infant Study of congenital cardiovascular malformations supports the observation that “syndromic” ECD tends to be of the complete atrioventricular canal type and is less frequently associated with left cardiac anomalies than the isolated form. However, each syndrome has a unique impact on the overall cardiovascular “phenotype,” including the ECD. This is especially true for Down and Ivemark syndromes, which are most frequently associated with ECD, but also for other syndromes as well. It is also suggested that isolated ECD is specifically associated with gastrointestinal and urinary tract anomalies. However, in Down syndrome ECD appears to be a specific cardiovascular expression of the trisomic state that is unrelated to other noncardiac malformations. Additional information on the association of ECD with other less common genetic syndromes is needed in order to further investigate the possible genetic basis of this cardiac defect. © 1992 Wiley-Liss, Inc.     

Mechanical and thermal behaviour of networks with “flexible” and “rigid” chains

“Rigid-rod” telechelics were synthesized via repetitive Diels-Alder reaction of biscyclohexadienes and bis(1,2,4-triazoline-3,5-diones). The bistriazolinediones were used in slight excess. The rigidity of the building blocks and the molecular weight were varied. Various amounts of these reactive telechelics are used to crosslink cis-1,4-polybutadiene. The mechanical and the thermal properties of these two-component networks were investigated by stress-strain, differential scanning calorimetry and dynamic-mechanical measurements. The occurrence of microphase separation between the “rigid” and the “flexible” components is discussed to explain the properties of these materials.