Double incretin receptor knock-out (DIRKO) mice present with alterations of trabecular and cortical micromorphology and bone strength.

UNLABELLED: A role for gut hormone in bone physiology has been suspected. We evidenced alterations of microstructural morphology (trabecular and cortical) and bone strength (both at the whole-bone--and tissue-level) in double incretin receptor knock-out (DIRKO) mice as compared to wild-type littermates. These results support a role for gut hormones in bone physiology. INTRODUCTION: The two incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), have been shown to control bone remodeling and strength. However, lessons from single incretin receptor knock-out mice highlighted a compensatory mechanism induced by elevated sensitivity to the other gut hormone. As such, it is unclear whether the bone alterations observed in GIP or GLP-1 receptor deficient animals resulted from the lack of a functional gut hormone receptor, or by higher sensitivity for the other gut hormone. The aims of the present study were to investigate the bone microstructural morphology, as well as bone tissue properties, in double incretin receptor knock-out (DIRKO) mice. METHODS: Twenty-six-week-old DIRKO mice were age- and sex-matched with wild-type (WT) littermates. Bone microstructural morphology was assessed at the femur by microCT and quantitative X-ray imaging, while tissue properties were investigated by quantitative backscattered electron imaging and Fourier-transformed infrared microscopy. Bone mechanical response was assessed at the whole-bone- and tissue-level by 3-point bending and nanoindentation, respectively. RESULTS: As compared to WT animals, DIRKO mice presented significant augmentations in trabecular bone mass and trabecular number whereas bone outer diameter, cortical thickness, and cortical area were reduced. At the whole-bone-level, yield stress, ultimate stress, and post-yield work to fracture were significantly reduced in DIRKO animals. At the tissue-level, only collagen maturity was reduced by 9 % in DIRKO mice leading to reductions in maximum load, hardness, and dissipated energy. CONCLUSIONS: This study demonstrated the critical role of gut hormones in controlling bone microstructural morphology and tissue properties.

Effect of bariatric surgery on cardiac function in obese patients: An echocardiographic assessment.

OBJECTIVES: To analyze the clinical and echocardiographic changes in individuals with morbid obesity who underwent bariatric surgery. METHODS: In total, 59 obese patients with body mass index >35 kg/m2 were prospectively enrolled. We assessed baseline pre-operative and a 6-month post-operative lipid profile, hemoglobin A1c, echocardiography, lifetime, and a 10-year risks of atherosclerotic disease for all patients. RESULTS: The mean patients' age was 37±12 years, with 40 (67.8%) women. We found that the pre-operative total cholesterol (4.2±1.1 vs. 4.4±1.1, p=0.014) and triglyceride levels (1.4±0.7 vs. 1.8±0.8, p<0.0001) were significantly lower than post-operative levels, while post-operative high-density lipoprotein levels were significantly higher (1.5±0.5 vs. 1.2±0.3, p<0.0001). The calculated 10-year risk of atherosclerotic cardiovascular disease was significantly lower post-operatively (1.1±1.6% vs. 1.6±1.8%, p<0.0001). Echocardiography follow-up revealed that diastolic dysfunction was more prevalent pre-operatively than that post-operatively (41% vs. 10%, p<0.0001). Post-operative left ventricular (LV) mass was significantly lesser than the pre-operative mass (168±252 g vs. 187±255 g, p=0.019), whereas the post-operative LV diastolic (46.5±7 mm vs. 38.5±18 mm, p=0.002) and systolic dimensions (31±5 mm vs. 25±11 mm, p=0.001) were significantly smaller. CONCLUSION: Bariatric surgery resulted in a significant amelioration in lipid profile, reduction in LV mass, and LV cavity dimensions.

First permanent molars with accentuated line patterns: Assessment of childhood health in an urban complex of the fifth millennium before the present.

OBJECTIVES: The objectives are 1) to calculate the position of highly accentuated lines in dental enamel of a group of individuals from Shahr-i-Sokhta, a thriving urban centre in Bronze Age South West Asia; 2) to identify peak frequencies of physiologically stressful periods during early childhood of these individuals; and 3) to relate these peak frequencies to developmental milestones at population level. DESIGN: We analysed highly accentuated lines in the enamel of nine (n = 9) permanent mandibular first molars of nine individuals from the 5th millennium before the present urban and long-distance-trading complex, Shahr-i Sokhta (Iran). Age at death ranged between 4.5 years and 18-20 years. Permanent mandibular first molar enamel begins to mineralise before birth, and is normally completed sometime between 2.1-3.3 years, giving us insight to early childhood physiological stress, the ages at which it occurs, and any peaks in the frequencies in highly accentuated line formation, through histological sections investigated using transmitted light microscopy. RESULTS: Highly accentuated line peak frequencies occur in the sample at c. four, nine, eleven, and twelve months. After 1 year of age, no more peaks occur. CONCLUSION: The peak frequencies coincide with the timing timing of the type of developmental milestones which may have exposed the individuals to an increased pathogen load, injury, or sub-optimal diet. We note similarity in peak timings in the few published, disparate populations, suggest a potential link with attainment of developmental milestones connected with morbidity, and propose reporting standardised statistics to enable exploration of differences between populations in terms of postnatal health-related stress.

Sensitivity of DiaRem Scoring System in Predicting Type Two Diabetes Mellitus Resolution After Bariatric Surgery in Qassim Region.

INTRODUCTION: Type two diabetes mellitus (T2DM) remission has been observed as an additional benefit of bariatric surgery for morbidly obese diabetic patients. There are many scoring systems for identifying factors that predict diabetes remission; however, there is as yet no universally applicable scoring system. AIM: This study aims to test the sensitivity of the DiaRem scoring system for predicting the resolution of T2DM in morbidly obese patients who underwent bariatric surgery at King Fahad Specialist Hospital in Buraydah, Saudi Arabia. METHODS:  This was a non-randomized controlled trial conducted at King Fahd Specialist Hospital in Buraydah, Saudi Arabia. Visiting patients at first screening were enrolled based on eligibility criteria. Data were collected according to the given parameters such as gender, age, body mass index (BMI), duration of diabetes mellitus (DM), medications (insulin, oral antihyperglycemic agents, number of tablets if used, or no medications use), presence of comorbidities, such as hypertension and dyslipidemia, HbA1c level (before surgery and at third, sixth, and 12th months after surgery), and fasting blood glucose (FBG) level (before and after surgery). RESULTS: A total of 96 diabetic patients were enrolled (35 males vs 61 females) with a mean age of 46.5 years. Laparoscopic sleeve gastrectomy was the most commonly performed surgery. The most common associated comorbidities were hypertension (50%) and hypothyroidism (14.6%). Results of the DiaRem scoring system showed 0-2 points in 15.6% patients, 3-7 points in 39.6% patients, 8-12 in 26% patients, 13-17 in 9.4% patients, and 18-22 in 9.4% patients. The lowest DiaRem score was associated with a higher value of BMI, shorter DM duration, and lower mean values of HbA1c and FBG post-surgery. CONCLUSION: Consistent with the literature, our results indicated that those with an increased BMI, shorter duration of DM, and lower values of HbA1c post-FBG had a greater chance of diabetes remission postoperatively.

Renal elimination of some 99mTc-labelled cysteamine derivatives.

It is generally believed that -CO-NH-(CH2)n-COOH moiety promotes tubular excretion of organic anions. Recently it was reported that newly developed renal agents, containing the oxotechnetium(V) glycine group, may mimic the carbonyl amide sequence of [131]I-o-iodohippuric acid. In this study the renal excretion of certain carboxy-cysteamine derivatives is investigated in mice, in the presence of renal tubular transport inhibitor. A similar pattern of renal depression was observed for complexes containing the oxotechnetium glycine sequence, suggesting that this group may satisfy structural parameters for tubular secretion of anionic technetium complexes.

A new approach to the synthesis of chiral blocks for cyclopentanoids.

A microreview is presented of the development by the authors of the original preparation of enantiomerically pure cyclopentane blocks from the racemic [2+2]-cycloadducts of 1,3-cyclopentadiene and its derivatives with dichloroketene.

Expression of VCAM-1 (CD106) by a subset of TCR gamma delta-bearing lymphocyte clones. Involvement of a metalloprotease in the specific hydrolytic release of the soluble isoform.

The cytokine-inducible vascular cell adhesion molecule 1/CD106 is widely distributed in endothelial, epithelial, macrophage, and dentritic cells. We previously have reported a mAb termed sTA that recognizes the CD106 molecule on various TCR gamma delta T cell clones that do not proliferate in response to an anti-CD3 stimulation. In the present report, further biochemical analysis reveals two intracellular precursors (82 and 98 kDa) of the membrane-bound 110-kDa form of CD106. In addition, we detect a 100-kDa soluble form in the culture supernatant of the specific cloned lymphocytes. Phorbol ester raises the amount of the soluble CD106 in the supernatant while simultaneously inducing the disappearance of the membrane-bound form. We show that the membrane-anchored form of CD106 is converted to soluble form by a regulated proteolytic cleavage process involving a metalloprotease. EDTA and 1,10-phenanthroline, two potent inhibitors of metalloproteases, specifically inhibit the conversion of the membrane anchored to the soluble form of the CD106 molecule. In fact, these results implicate a Zn(2+)-activated metalloprotease in the regulation of CD106 expression in a subset of T cells and, therefore, represent a novel pathway of T cell functions.

Desenvolvimento neuropsicomotor de lactentes desnutridos / Neuropsychomotor development of malnourished babies

OBJETIVOS: O objetivo deste estudo foi analisar o desenvolvimento neuropsicomotor de lactentes com desnutrição leve e caracterizar seu perfil nutricional. MÉTODOS: A pesquisa foi do tipo transversal, numa população de 374 lactentes e amostra de 31 desnutridos leve, entre 7 e 24 meses de idade, matriculados em creches municipais. O estado nutricional foi identificado pelo critério de Gómez e caracterizado por um questionário. Para a avaliação neuropsicomotora utilizou-se a Escala de Desenvolvimento Psicomotor da Primeira Infância de Brunet e Lézine. RESULTADOS: Os principais resultados do questionário mostraram: infecções respiratórias (48,4 por cento); diarréias (71,0 por cento); pais em união estável (61,3 por cento); pais com ensino fundamental incompleto (74,2 por cento das mães, 83,8 por cento dos pais); renda familiar de 1 a 3 salários-mínimos (80,6 por cento); aleitamento materno satisfatório (67,7 por cento); reação adversa a algum alimento (41,9 por cento). Entre os dados neuropsicomotores, as médias das Idades de Desenvolvimento da Linguagem (14,45 meses) e da Sociabilidade (14,74 meses) foram as que obtiveram os valores mais abaixo da média da Idade Cronológica (16,41 meses). Todas as áreas avaliadas obtiveram Quocientes de Desenvolvimento dentro da normalidade, porém, as áreas da Linguagem e da Sociabilidade foram classificadas em nível "normal baixo" e as outras em nível "normal médio". CONCLUSÕES: A avaliação neuropsicomotora é instrumento fundamental na assistência ao lactente desnutrido, que tende a apresentar deficiências nas áreas da Linguagem e Sociabilidade, fornecendo subsídios para observar sua atuação exploratória, efeito de seu pensamento, e planejar o trabalho intervencionista.