Examining Arginase-1 Trimerization Uncovers a Promising Allosteric Site for Inhibition.

Arginase-1 (ARG-1) is a promising target for cancer immunotherapy, but the small size and the highly polar nature of its catalytic site present significant challenges for inhibitor development. An alternative strategy to induce enzyme inhibition by targeting protein oligomerization has been developed recently, offering several advantages such as increased selectivity, promotion of protein degradation, and potential substoichiometric inhibition. In this study, we demonstrated that only trimeric ARG-1 is active, which was confirmed by producing monomeric arginase-1.

Bioanalysis of tucatinib and metabolite, and a five-way cross-validation to support clinical pharmacokinetic analysis.

Tucatinib, a tyrosine kinase inhibitor of HER2, is approved in multiple regions for metastatic breast cancer and is being evaluated in metastatic colorectal and gastric cancers. During clinical development, quantification of tucatinib plasma concentrations for pharmacokinetic analysis was performed using MS/MS analysis by three laboratories using five different methods. Cross-validation was required to confirm data across laboratories were comparable.

Tucatinib Inhibits Renal Transporters OCT2 and MATE Without Impacting Renal Function in Healthy Subjects.

Tucatinib is a potent tyrosine kinase inhibitor selective for human epidermal growth factor receptor 2 (HER2) approved by the US Food and Drug Administration for the treatment of HER2-positive metastatic breast cancer and in development for other HER2-positive solid tumors. Modest, reversible serum creatinine (SCr) elevations have been observed in tucatinib clinical trials. SCr is conveyed by the renal drug transporters organic cation transporter 2 (OCT2) and multidrug and toxin extrusion protein 1 (MATE1) and 2-K (MATE2-K) and can increase in the presence of inhibitors of these transporters.

Pregnancy outcome following frozen embryo transfer after artificial cycle or treatment by clomiphene citrate.

The optimal method to prepare endometrium before frozen embryo transfer (FET) is not yet established. We retrospectively studied 4496 FET and detailed pregnancy and miscarriage rates in three groups of patients according to the endometrium preparation they have followed before their successive FET: clomifene citrate (CC, group 1), artificial cycle (AC, group 2) or switch between CC and AC (group 3). The overall pregnancy rates per transfer were 24.

Modeling Sources of Teaching Self-Efficacy for Science, Technology, Engineering, and Mathematics Graduate Teaching Assistants.

Graduate teaching assistants (GTAs) in science, technology, engineering, and mathematics (STEM) have a large impact on undergraduate instruction but are often poorly prepared to teach. Teaching self-efficacy, an instructor's belief in his or her ability to teach specific student populations a specific subject, is an important predictor of teaching skill and student achievement. A model of sources of teaching self-efficacy is developed from the GTA literature.

Soliciting stakeholders' views on the organization of child and adolescent mental health services: a system in trouble.

Background: Despite a high prevalence of mental health problems among children and adolescents Belgium, like many other Western countries, does not have a clear strategy for the organization of child and adolescent mental healthcare services (CAMHS).

Methods: This paper describes stakeholders' views on the organization of CAMHS based on a qualitative study. Ten in-depth interviews with high profile stakeholders were complemented by roundtable discussions (n = 30).

Recommendations for the organization of mental health services for children and adolescents in Belgium: use of the soft systems methodology.

The prevalence of mental health problems among children and adolescents in Western countries is high. Belgium, like many other Western countries, struggles with the set-up of a coherent and effective strategy for dealing with this complex societal problem. This paper describes the development of a policy scenario for the organization of child and adolescent mental health care services (CAMHS) in Belgium.

[Adenomyosis].

Adenomyosis is a medical benign condition of the endometrium-myometrium interface that is histopathologically characterized by the presence of ectopic tissue (endometrial glands and stroma) in myometrium. The diagnosis is complicated by the low specificity of its symptoms and the frequent associations with others gynaecologic pathologies. Consequently, paraclinic investigations are essential to make the diagnosis.

The rising demand for consultation-liaison psychiatry for older people: comparisons within Liverpool and the literature across time.

Objectives: To compare the rate of referrals of older people for consultation-liaison psychiatry services over time within Liverpool and with the literature.

Methods: All referrals to the liaison psychiatry service for older people in Liverpool between 1999 and 2004 were used to calculate referral rates and compared with data from the same hospital from 1981 to 1989 previously published. Data related to referral rates was extracted from other published studies to allow cross-national comparisons over time.

[A non frequent cause of kidney disease].

The EDTA (European Dialysis and Transplantation Association) statistic data on kidney diseases in ageing population point out vascular and/or metabolic origins. We report here a case of a rare cause of renal insufficiency, a Gougerot-Sjögren primary syndrome, diagnosed in an old patient. Renal and salivary gland biopsies were performed.

A novel acetabular alignment guide for THR using selective anatomic landmarks on the pelvis.

This paper presents a novel approach for acetabular alignment during the implant of a prosthetic hip joint in a natural pelvis. The alignment instrument uses selective anatomic bony landmarks on the pelvis, which are accessible in surgery, to guide the placement of the acetabular component in the appropriate orientation. A closed form solution, involving both a forward and reverse analysis, is presented to relate the parameters of the device with the abduction and anteversion angles.

[How I investigate ... Alport's syndrome by skin biopsy. When the skin speaks for the kidney].

Alport's syndrome is a severe hereditary renal disease. Type IV collagen is abnormal in its molecular composition both in the kidneys and the skin. Immunohistochemistry performed on a conventional skin biopsy allows to prove the diagnosis in the affected subjects and in healthy women exhibiting the mutation on a single X chromosome.

[Pituitary diseases in elderly patients with chronic renal insufficiency].

Chronic renal failure (CRF) in the elderly is a cause of multiple endocrine dysfunctions. The three most common pituitary axes involved are the thyrotrope, lactotrope and gonadotrope axes. Thyroid dysfunction may be the consequence of thyroid or pituitary failure.

[Clinical case of the month. A new case of nephropathia epidemica due to Puumala virus].

Nephropathia epidemica due to Puumala virus has already been described in Belgium. Its evolution is usually favourable. The main symptoms are fever, a decrease platelet count, proteinuria and acute renal insufficiency, which, in an epidemiological context, quickly point the correct diagnosis.

[Acute tubulo-interstitial nephropathy with uveitis: apropos of case].

We report another case of acute interstitial nephritis with uveitis (TINU syndrome) in a 35-year-old woman. About thirty cases were described since the first ones 20 years ago. We discuss the assessment needed to reach the diagnosis.

Possible pathogenic role of IgE in Henoch-Schönlein purpura.

The incidences of clinical and biological markers of atopy were investigated in 16 children with IgA nephropathy (IgAN) (group A) and in 22 with Henoch-Schönlein purpura nephritis (HSPN) (group B). The incidence of increased plasma IgE levels according to age-matched normal values was significantly higher in group B (17/22, 77%) than in group A (7/16, 44%) (P < 0.05).

[Acute experimental glomerulonephritis induced by the glomerular deposition of circulating polymeric IgA-concanavalin A complexes].

The perfusion of polymeric IgA (pIgA)--or secretory IgA (sIgA)--Concanavalin A (ConA) non-immune complexes (apparent Mol.Wt greater than 10(3) Kd) into the aorta of rats led to a dose-dependent and a mannose-dependent deposition of both IgA and lectin into the glomeruli. Rats injected with amounts of those complexes as low as 500 micrograms developed, one hour later, a focal and segmental proliferative glomerulonephritis characterized by: a) the deposition in the mesangial area of most glomeruli of injected complexes and of rat C3; b) small areas of fibrinoïd necrosis in 10 to 15% of glomeruli, confined to the periphery of a single lobule of the tuft; c) a segmental infiltration of those glomeruli by polymorphonuclear leucocytes, mononuclear phagocytes and platelets; d) a hyperactive aspect of mesangial cells; e) the presence of red blood cells in tubular lumens.