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\"The body is the most complex machine in the world, and the only one for which you cannot get a replacement part from the manufacturer. For centuries, medicine has reached for what's available--sculpting noses from brass, borrowing skin from frogs and hearts from pigs, crafting eye parts from jet canopies and breasts from petroleum by-products. Today we're attempting to grow body parts from scratch using stem cells and 3D printers. How are we doing? Are we there yet? In Replaceable You, Mary Roach explores the remarkable advances and difficult questions prompted by the human body's failings. When and how does a person decide they'd be better off with a prosthetic than their existing limb? Can a donated heart be made to beat forever? Can an intestine provide a workable substitute for a vagina? Roach dives in with her characteristic verve and infectious wit. Her travels take her to the OR at a legendary burn unit in Boston, a \"superclean\" xeno-pigsty in China, and a stem cell \"hair nursery\" in the San Diego tech hub. She talks with researchers and surgeons, amputees and ostomates, printers of kidneys and designers of wearable organs. She spends time in a working iron lung from the 1950s, stays up all night with recovery techs as they disassemble and reassemble a tissue donor, and travels across Mongolia with the cataract surgeons of Orbis International. Irrepressible and accessible, Replaceable You immerses readers in the wondrous, improbable, and surreal quest to build a new you\"-- Dust jacket flap.

The principles and applications of optical elastography for use in biological imaging are reviewed. Optical elastography, the use of optics to characterize and map the mechanical properties of biological tissue, involves measuring the deformation of tissue in response to a load. Such measurements may be used to form an image of a mechanical property, often elastic modulus, with the resulting mechanical contrast complementary to the more familiar optical contrast. Optical elastography is experiencing new impetus in response to developments in the closely related fields of cell mechanics and medical imaging, aided by advances in photonics technology, and through probing the microscale between that of cells and whole tissues. Two techniques — optical coherence elastography and Brillouin microscopy — have recently shown particular promise for medical applications, such as in ophthalmology and oncology, and as new techniques in cell mechanics.

Background/Objectives: The population of the obese is increasing worldwide. Prevention and improvement of obesity are indispensable for decreasing the risk of metabolic disorders. We have recently shown that obesity and fatty liver are reduced by a plant-derived lactic acid bacterium, Pediococcus pentosaceus LP28 (LP28), in high-fat diet-induced obese mice. The aim of the present clinical study is to prove that LP28 is effective for reducing body fat and body weight, as shown in the experiment using mice. Subjects/Methods: The clinical trial was carried out as a double-blind, randomized, placebo-controlled study comprising 62 subjects (20–70 years of age, BMI 25–30 kg/m 2 ). These subjects were randomly assigned to three groups that received living LP28, heat-killed LP28 or a placebo powder, administered orally once a day for 12 weeks. Results: Heat-killed LP28 reduced BMI (0.45 kg/m 2 , 95% CI (0.04, 0.86), P =0.035), body fat percentage (1.11%, (0.39, 1.82), P =0.002), body fat mass (1.17 kg (0.43, 1.92), P =0.004) and waist circumference (2.84 cm (0.74, 4.93), P =0.009) when compared with a placebo group. Fasting plasma glucose, HbA1c, fasting insulin, HOMA-IR and serum lipids levels did not change by either living LP28 or heat-killed LP28 intake. Conclusions: Heat-killed LP28 displays an antiobesity effect that reduces BMI, body fat and waist circumference, suggesting that the plant-derived lactic acid bacterium LP28 would be a promising preventive of metabolic syndrome.

Use of probiotic supplements, the benefits of which have not been proven in sportspeople, is becoming more widespread among runners. The aim of this study was to evaluate the effect of a multi-strain probiotic on body composition, cardiorespiratory fitness and inflammation in the body. The randomised, double-blind study included 66 long-distance runners. The intervention factor was a multi-strain probiotic or placebo. At the initial and final stages of the study, evaluation of body composition and cardiorespiratory fitness was performed and the presence of inflammation determined. In the group of men using the probiotic, an increase in lean body mass (p = 0.019) and skeletal muscle mass (p = 0.022) was demonstrated, while in the group of women taking the probiotic, a decrease in the content of total body fat (p = 0.600) and visceral fat (p = 0.247) was observed. Maximum oxygen consumption (VO2max) increased in women (p = 0.140) and men (p = 0.017) using the probiotic. Concentration of tumour necrosis factor-alpha decreased in women (p = 0.003) and men (p = 0.001) using the probiotic and in women (p = 0.074) and men (p = 0.016) using the placebo. Probiotic therapy had a positive effect on selected parameters of body composition and cardiorespiratory fitness of study participants and showed a tendency to reduce inflammation.

Background: It is commonly stated in the literature on human exposure to bisphenol A (BPA) that food is the predominant BPA exposure source, and that BPA is rapidly and completely cleared from the body. If this is correct, BPA levels in fasting individuals should decrease with increased fasting time. Objectives: We set out to investigate the relationship between urine BPA concentration and fasting time in a population-based sample. Methods: We modeled log BPA urine concentration as a function of fasting time, adjusted for urine creatinine and other confounders, in 1,469 adult participants in the 2003-2004 National Health and Nutrition Examination Survey. We estimated the BPA \"population-based half-life\"$({\\rm pop}^{{\\textstyle\\frac{1}{2}}})$for a fasting time of 0-24 hr, < 4.5 hr, 4.5-8.5 hr, and > 8.5 hr. Results: The overall${\\rm pop}^{{\\textstyle\\frac{1}{2}}}$for the 0- to 24-hr interval was 43 hr [95% confidence interval (CI), 26-119 hr]. Among those reporting fasting times of 4.5-8.5 hr (n = 441), BPA declined significantly with fasting time, with a${\\rm pop}^{{\\textstyle\\frac{1}{2}}}$of 4.1 hr (95% CI, 2.6-10.6 hr). However, within the fasting time intervals of 0-4.5 hr (n = 129) and 8.5-24 hr (n = 899), we saw no appreciable decline. Fasting time did not significantly predict highest (> 12 ng/mL) or lowest (below limit of detection) BPA levels. Conclusions: Overall, BPA levels did not decline rapidly with fasting time in this sample. This suggests substantial nonfood exposure, accumulation in body tissues such as fat, or both. Explaining these findings may require experimental pharmacokinetic studies of chronic BPA exposure, further examination of BPA levels and effects in fat, and a search for important nonfood sources.

Cells in tissues communicate by secreted growth factors (GF) and other signals. An important function of cell circuits is tissue homeostasis: maintaining proper balance between the amounts of different cell types. Homeostasis requires negative feedback on the GFs, to avoid a runaway situation in which cells stimulate each other and grow without control. Feedback can be obtained in at least two ways: endocytosis in which a cell removes its cognate GF by internalization and cross-inhibition in which a GF down-regulates the production of another GF. Here we ask whether there are design principles for cell circuits to achieve tissue homeostasis. We develop an analytically solvable framework for circuits with multiple cell types and find that feedback by endocytosis is far more robust to parameter variation and has faster responses than cross-inhibition. Endocytosis, which is found ubiquitously across tissues, can even provide homeostasis to three and four communicating cell types. These design principles form a conceptual basis for how tissues maintain a healthy balance of cell types and how balance may be disrupted in diseases such as degeneration and fibrosis.

Abstract Objective To explore depot-specific functional aspects of adipose tissue, examining the putative role for menopause and HIV status on insulin sensitivity (SI) and beta-cell function in Black South African women. Methods Women (n = 92) from the Middle-Aged Soweto Cohort, including premenopausal HIV-negative women (n = 21); premenopausal women living with HIV (LWH; n = 11); postmenopausal HIV-negative women (n = 42); and postmenopausal women LWH (n = 18) underwent the following tests: body composition (dual-energy x-ray absorptiometry); fasting bloods for sex hormones, inflammation, and adipokines; frequently sampled intravenous glucose tolerance test for SI and beta-cell function (disposition index, DI); abdominal (aSAT) and gluteal subcutaneous adipose tissue (gSAT) biopsies for cell size, and mRNA expression of adipokines, inflammation, and estrogen receptors (ER). Results Depot-specific associations between gene expression and insulin parameters did not differ by HIV or menopause status. Pooled analysis showed significant models for SI (P = .002) and DI (P = .003). Higher SI was associated with lower leptin and CD11c expression in aSAT and higher adiponectin in gSAT. Higher DI was associated with higher aSAT and gSAT expression of adiponectin, lipoprotein lipase, ERα, and PPARγ, and lower leptin in aSAT. Women LWH had higher expression of adiponectin and lower expression of leptin in both aSAT (P = .002 and P = .005) and gSAT (P = .004 and P = .002), respectively, and a larger proportion of smaller cells in aSAT (P < .001). Conclusion Insulin sensitivity and beta-cell function were distinctively associated with aSAT and gSAT. While menopause did not influence these relationships, HIV had a significant effect on adipose tissue, characterized by variations in cell size distribution and transcript levels within the depots.

Abstract Background Delafloxacin is an oral or intravenous (IV) antibiotic indicated for the treatment of acute bacterial skin and skin structure infections (ABSSSI), including both gram-positive (including methicillin-resistant Staphylococcus aureus [MRSA]) and gram-negative organisms. Chemically distinct from other quinolones, delafloxacin exhibits enhanced potency, particularly against gram-positive pathogens. The integration of efficacy data across the Phase III ABSSSI studies is presented here and allows for additional examination of results across subgroups. Methods Results of 2 multicenter, randomized, double-blind trials of 1510 adults with ABSSSI were pooled for this analysis. Subjects in the vancomycin arm received 15 mg/kg, plus 1-2 g of aztreonam every 12 hours. Delafloxacin was dosed at 300 mg IV every 12 hours in Study 302; dosing in Study 303 was 300 mg IV every 12 hours for 3 days, with a mandatory, blinded switch to delafloxacin at 450 mg orally every 12 hours. The primary endpoint was objective response (OR), defined as a ≥20% reduction of lesion spread of erythema area at the primary infection site at 48 to 72 hours (±2 hours), in the absence of clinical failure. Investigator-assessed response, based on the resolution of signs and symptoms at follow-up (FU; Day 14 ± 1) and late follow-up (LFU; Day 21- 28), were secondary endpoints. Results In the intent-to-treat analysis set, the OR was 81.3% in the delafloxacin arm and 80.7% in the comparator arm (mean treatment difference 0.8%, 95% confidence interval -3.2% to 4.7). Results for OR in the defined subgroups showed delafloxacin to be comparable to vancomycin/aztreonam. Investigator-assessed success was similar at FU (84.7% versus 84.1%) and LFU (82.0% versus 81.7%). Delafloxacin was comparable to vancomycin/aztreonam in the eradication of MRSA, at 98.1% versus 98.0%, respectively, at FU. The frequencies of treatment-emergent adverse events between the groups were similar. Conclusions Overall, IV/oral delafloxacin fixed-dose monotherapy was non-inferior to IV vancomycin/aztreonam combination therapy and was well tolerated in each Phase III study, as well as in the pooled analysis, regardless of endpoint or analysis population.

Obesity is an important risk factor for the development of metabolic syndrome disorders. We previously showed that the liver fatty acid-binding protein null mouse (LFABP−/−) becomes obese upon high-fat diet (HFD) feeding but remains metabolically healthy. Here, we find that the obese LFABP−/− mouse increases subcutaneous adipose tissue (SAT) mass by markedly increasing the number rather than the size of adipocytes, as is typical with HFD. Indeed, while HFD-fed LFABP−/− mice had almost double the fat mass of WT, SAT adipocyte size was >4-fold smaller and adipocyte number was 5-fold higher in the LFABP−/−. Transcriptomic analysis of SAT revealed that Lfabp deletion alters the expression of multiple pathways that modulate adipose expansion and function including cholesterol biosynthesis, adipogenesis, and extracellular matrix remodeling. LFABP is expressed in the liver and small intestine but not in adipose tissues; thus, its ablation may promote interorgan crosstalk that drives the hyperplastic expansion of metabolically beneficial SAT, contributing to the healthy obese phenotype of the LFABP−/− mouse.

Immune responses in human tissues rely on the concerted action of different cell types. Inter-cellular communication shapes both the function of the multicellular interaction networks and the fate of the individual cells that comprise them. With the advent of new methods to profile and experimentally perturb primary human tissues, we are now in a position to systematically identify and mechanistically dissect these cell-cell interactions and their modulators. Here, we introduce the concept of multicellular hubs, functional modules of immune responses in tissues. We outline a roadmap to discover multicellular hubs in human tissues and discuss how emerging technologies may further accelerate progress in this field.