[Important alteration of the Dutch treatment algorithm in patients with type 2 diabetes mellitus]. / Belangrijke wijziging van behandelrichtlijn 'Diabetes mellitus type 2'.

Recent trials of two classes of glucose-lowering drugs (SGLT2 inhibitors and GLP1RAs) have shown consistent cardiovascular and renal benefits that appear independent of glycaemic control. These results have prompted the Dutch College of General Practitioners (NHG) together with the Dutch Society of Internal Medicine (NIV) to update the treatment algorithm in patients with type 2 diabetes mellitus (T2D) at very high CVD risk. The use of SGLT2 inhibitors or GLP1RAs is now recommended in 3 groups of people with T2D. 1. patients with established CVD; 2. Patients with chronic kidney disease and a moderately to high CVD risk according to KDIGO; 3. patients with heart failure with reduced ejection fraction (HFrEF). Treatment algorithms differ for drug-naïve and drug-treated patients with T2D. In both drug-naïve and drug-treated patients the use of a SGLT2 inhibitor respectively as monotherapy or add-on is recommended as first step. If HbA1c is above the individual target, metformin will be added in drug-naive patients whereas GLP1-RAs could be considered in drug-treated patients. GLP1-RAs should also be considered when SGLT2-inhibitors are contraindicated.

Comparison of three methods for competitive binding of monoclonal antibodies. The localization of antigenic sites for monoclonal antibodies on Panulirus interruptus hemocyanin.

The competitive binding of a panel of monoclonal antibodies against hemocyanin of Panulirus interruptus hemocyanin was investigated with three different methods. A competitive-binding immunoassay method was more successful in the determination of ternary complexes than gel electrophoresis and gel filtration. The latter two methods could only be applied with antibodies possessing a higher affinity. Eleven monoclonal antibodies were assigned to groups on the basis of their interactions with five antigenic regions.

Identification of two antibody-interaction sites on the surface of Panulirus interruptus hemocyanin.

Negatively stained complexes of Panulirus interruptus (spiny lobster) hemocyanin with two different monoclonal antibodies, named E and J, were studied by electron microscopy and image processing. The attachment site of the antibodies to the hexameric hemocyanin molecule was deduced from two perpendicular views of hemocyanin/antibody complexes, in which either the threefold axis or one of the twofold axes was oriented perpendicular to the supporting film. Images of complexes in these orientations were searched with reference images simulated from the known X-ray structure of P. interruptus hemocyanin. The two sites were further characterized by combining our results from electron microscopy with structural data obtained by X-ray diffraction and other methods. These two antibodies recognize different non-overlapping epitopes. The epitope for clone E is located on domain 3 at the surface of the beta barrel and consists of certain loops, which form connections between beta-strand structures. The epitope for clone J is situated on domain 1 at the surface of an alpha-helical region and consists mainly of certain alpha-helices connecting loops. The orientation of the hemocyanin hexamers in the two complexes is very different, as is demonstrated most clearly when they form chains. Clone E forms complexes with the threefold axes perpendicular to the chain direction, while for clone J the threefold axes seem to be parallel to the main direction. The angle between the Fab part of an IgG molecule and the threefold axis of the hexamer is 60 +/- 5 degrees for clone E and 35 +/- 7 degrees for clone J. This observation is clearly related to the difference in orientation of the hexamers for the two complexes.

Some multivariate tests for differences in sexual dimorphism between human populations.

Two multivariate statistical tests are presented for examining differences in sexual dimorphism between human populations. One test refers to general differences in sexual dimorphism; the other, only to differences in size aspects of sexual dimorphism. There is no current resolution to the complementary problem of testing for differences of direction in sexual dimorphism. By applying the tests to a comparison of sexual dimorphism in 26 samples of skulls from a world-wide distribution of human populations, significant results (at alpha = 0.05) were found in the majority of cases with the general test, and in a minority of cases with the size test.