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The development of trust in testimony is discussed. Topics include neglect of the role of testimony in cognitive development, children's sensitivity to sources of information, representation of information from different sources, the intertwining of different sources of information, and the development of trust.

The transverse upper gracilis (TUG) flap provides a good alternative to the gold standard DIEP in breast reconstruction. However, flap volume estimates are subjective, making preoperative planning potentially challenging. To derive a reliable, accurate, and reproducible mathematical algorithm for the preoperative calculation of TUG flap volumes. Nineteen consecutive patients with 30 TUG flaps were prospectively included. On the assumption that the TUG flap resembles two isosceles prisms, the formula of the volume of a prism was used to calculate their preoperative flap weights. These were then intraoperatively compared to the actual flap weights. A regression equation was calculated from the correlation analysis of 10 random flaps. This was then applied to the remaining 20 flaps to assess for improved reliability and weight prediction accuracy. The prism volume equation used to clinically calculate flap volumes was: Geometric flap weight = (h 1 bT)/2+ (h 2 bT)/2, (h = height, b = base, T = flap thickness); all in centimetres. Geometric and actual flap weights were found to be significantly correlated (r2 = 0.977) generating the following regression formula: predicted TUG weight = 0.924 × geometric weight + 26.601. When this was applied to the remaining 20 flaps, no significant difference was found (p = 0.625) between predicted and actual flap weights, demonstrating an increased accuracy of predicting flap volume. The proposed formula provides the clinician with a more accurate and reliable estimation of available TUG flap volume and may potentially aid with preoperative planning and patient consultations. [ABSTRACT FROM AUTHOR]

Background and Aims: Insulin-like growth factor (IGF)-1 deficiency is associated with a range of metabolic disorders. Cyclic glycine-proline (cGP) is a natural nutrient and regulates the amount of active IGF-1 in plasma. Plasma cGP decreases in hypertensive women whereas increases in obese women, suggesting its involvement in cardio-metabolic function. We therefore examined the effects of cGP on metabolic profiles and blood pressure in high-fat diet (HFD)-induced obese male rats.Methods: Male rats were fed either a HFD or a standard chow diet (STD) ad-libitum from 3 to 15 weeks of age. Rats were administered either saline or cGP from 11 to 15 weeks of age. At 14 weeks of age, systolic-blood pressure (SBP) was measured by tail-cuff plethysmography and body composition quantified by DEXA. Blood and retroperitoneal fat tissues were collected. Plasma concentrations of insulin, IGF-1, IGF binding protein (IGFBP)-3 and cGP were evaluated using ELISA and HPLC-MS respectively.Results: Compared to STD, HFD feeding increased SBP, total fat mass and fat/lean ratio, retroperitoneal fat weight, fasting plasma insulin and cGP concentrations whereas decreased plasma IGF-1 and IGFBP-3 concentrations. Administration of cGP reduced SBP and retroperitoneal fat weight, but had no effect on body composition and plasma insulin concentrations.Conclusion: HFD-associated decreases in IGFBP-3 and increases in cGP represent an autocrine response to normalize IGF-1 function through improving the amount of bioavailable IGF-1 in the circulation of obese male rats. The beneficial effects of cGP on SBP and retroperitoneal fat mass may suggest a therapeutic potential for cGP in HFD-associated cardio-metabolic complications. [ABSTRACT FROM AUTHOR]

Abstract Objective We hypothesized that DA and L-DOPA derived from nutritional tyrosine and the resultant observed postprandial plasma excursions of L-DOPA and DA might affect glucose tolerance via their ability to be taken-up by beta cells and inhibit glucose-stimulated β-cell insulin secretion. Methods To investigate a possible circuit between meal-stimulated 3,4-dihydroxy-L-phenylalanine (L-DOPA) and dopamine (DA) production in the GI tract and pancreatic β-cells, we: 1) mapped GI mucosal expression of tyrosine hydroxylase (TH) and aromatic amino acid decarboxylase (AADC); 2) measured L-DOPA and DA content of GI mucosal tissues following meal challenges with different L-tyrosine (TYR) content, 3) determined whether meal TYR content impacts plasma insulin and glucose excursions; and 4) characterized postprandial plasma excursions of L-DOPA and DA in response to meal tyrosine content in rodents and a population of bariatric surgery patients. Next, we characterized: 1) the metabolic transformation of TYR and L-DOPA into DA in vitro using purified islet tissue; 2) the metabolic transformation of orally administrated stable isotope labeled TYR into pancreatic DA, and 3) using a nuclear medicine technique, we studied endocrine beta cells in situ release and binding of DA in response to a glucose challenge. Results We demonstrate in rodents that intestinal content and circulatory concentrations L-DOPA and DA, plasma glucose and insulin are responsive to the tyrosine (TYR) content of a test meal. Intestinal expression of two enzymes, Tyrosine hydroxylase (TH) and Aromatic Amino acid Decarboxylase (AADC), essential to the transformation of TYR to DA was mapped and the metabolism of metabolism of TYR to DA was traced in human islets and a rodent beta cell line in vitro and from gut to the pancreas in vivo. Lastly, we show that β cells secrete and bind DA in situ in response to glucose stimulation. Conclusions We provide proof-of-principle evidence for the existence of a novel postprandial circuit of glucose homeostasis dependent on nutritional tyrosine. DA and L-DOPA derived from nutritional tyrosine may serve to defend against hypoglycemia via inhibition of glucose-stimulated β-cell insulin secretion as proposed by the anti-incretin hypothesis. Graphical abstract Image 1 Schematic of the proposed gut to pancreas blood glucose concentration regulatory circuit. Abbreviations used: TH, tyrosine hydroxylase; AADC, Aromatic l-amino acid decarboxylase; L-DOPA, L-3,4-dihydroxyphenylalanine; D2R, Dopamine receptor type 2, DA, Dopamine; LAAT, L-Type Amino Acid Transporter 1; DAT, dopamine active transporter; VMAT2, Vesicular monoamine transporter type 2; GSIS, glucose-stimulated insulin secretion. Grey boxes show tissue bypassed by GS, Sleeve Gastrectomy, and RYGB, Roux-en-Y Gastric Bypass surgeries. Highlights • Nutritional tyrosine is metabolized to L DOPA and DA in the foregut. • Postprandial L-DOPA and DA plasma concentrations rise in response to tyrosine. • Oral stable isotope labeled tyrosine is found postprandially in the pancreas as DA. • L-DOPA and DA are inhibitors of beta cell glucose-stimulated insulin secretion. • Postprandial L-DOPA and DA excursions are muted in certain bariatric surgery patients. [ABSTRACT FROM AUTHOR]

Objective Regulation of energy balance depends on pro-opiomelanocortin (POMC)-derived peptides and melanocortin-4 receptor (MC4R). Alpha-melanocyte stimulating hormone (α-MSH) is the predicted natural POMC-derived peptide that regulates energy balance. Desacetyl-α-MSH, the precursor for α-MSH, is present in brain and blood. Desacetyl-α-MSH is considered to be unimportant for regulating energy balance despite being more potent (compared with α-MSH) at activating the appetite-regulating MC4R in vitro . Thus, the physiological role for desacetyl-α-MSH is still unclear. Methods We created a novel mouse model to determine whether desacetyl-α-MSH plays a role in regulating energy balance. We engineered a knock in targeted QKQR mutation in the POMC protein cleavage site that blocks the production of both desacetyl-α-MSH and α-MSH from adrenocorticotropin (ACTH 1-39 ). Results The mutant ACTH 1-39 (ACTH QKQR ) functions similar to native ACTH 1-39 (ACTH KKRR ) at the melanocortin 2 receptor (MC2R) in vivo and MC4R in vitro . Male and female homozygous mutant ACTH 1-39 ( Pomc tm1/tm1 ) mice develop the characteristic melanocortin obesity phenotype. Replacement of either desacetyl-α-MSH or α-MSH over 14 days into Pomc tm1/tm1 mouse brain significantly reverses excess body weight and fat mass gained compared to wild type (WT) ( Pomc wt/wt ) mice. Here, we identify both desacetyl-α-MSH and α-MSH peptides as regulators of energy balance and highlight a previously unappreciated physiological role for desacetyl-α-MSH. Conclusions Based on these data we propose that there is potential to exploit the naturally occurring POMC-derived peptides to treat obesity but this relies on first understanding the specific function(s) for desacetyl-α-MSH and α-MSH. [ABSTRACT FROM AUTHOR]

Summary Introduction Implant-based breast reconstruction has relatively high complication rates. Removal of infected implants and immediate autologous reconstruction is a safe single-stage procedure that preserves the native breast skin envelope. Methods A single-centre, retrospective proof-of-concept review of all salvage procedures performed for acute/chronic infected or exposed implant-based reconstructions by a single surgeon over a 6-year period. Results We present 13 cases of a particularly difficult subgroup of acute/chronic infection/extrusion over a 6-year period. All were successfully salvaged in a single procedure by implant removal and immediate free flap reconstruction with no significant complications. All patients had a change of pocket from subpectoral to subcutaneous and partial capsulectomies. Four patients had unilateral DIEP flaps for unilateral reconstruction, 3 bi-pedicle DIEP flaps for unilateral reconstruction, 2 bilateral TUG flaps for unilateral reconstruction, 3 bilateral DIEP flaps for bilateral reconstruction and 1 unilateral DIEP and implant for unilateral reconstruction. Conclusions These patients are often slim with limited donor sites and pose technical challenges, often requiring double free flap reconstructions. Single-stage implant removal and autologous reconstruction preserves the breast skin envelope to maximise cosmesis in a single procedure. The introduction of healthy, well-vascularised tissue may also help treat the infection. [ABSTRACT FROM AUTHOR]

Over that past decade, ecological restoration practices have expanded globally. However, the effectiveness of ecological restoration depends on the complex interactions of various natural and socioeconomic factors, about which there is limited scientific understanding and thus provides an important research frontier. This paper analyzed the relationship between regional scale vegetation restoration and the process of urbanization using the Loess Plateau of China as a case study. This region has experienced both rapid urbanization and a high number of vegetation restoration activities. Urbanization and vegetation restoration can be considered as extremes on the spectrum of environment preservation activities. Three separate spatial correlation analyses between urbanization and vegetation restoration were identified, resulting in: 1) insignificant correlations in saturated urban areas; 2) significant negative correlations in peri -urban areas; and 3) significant positive correlations in undeveloped areas. The relationship between urbanization and vegetation restoration is thus stage-dependent. Impacts of urbanization on vegetation degradation has improved but has not been fully addressed by large scale vegetation restoration. Regardless of whether the county or grid scale is used, peri -urbanization was found to be the critical factor affecting the effectiveness of vegetation restoration over both time and space. Therefore, peri -urbanized areas are viewed as priorities for improving the coupling of urban development and vegetation restoration. [ABSTRACT FROM AUTHOR]