Nature Medicine 18, 639 (2012). doi:10.1038/nm0512-639

Nature Medicine 18, 642 (2012). doi:10.1038/nm0512-642

Author: Elie Dolgin

Everyone from rock stars to nonagenarians experiences hearing loss, but no drugs have ever been approved specifically to prevent or treat this problem. Recently, a handful of drug companies have started to make some noise, with a number of experimental compounds now in human trials. Elie Dolgin sounds off on what could be a multibillion dollar market.

Nature Medicine 18, 646 (2012). doi:10.1038/nm0512-646

Authors: Tikki Pang & Laurie Garrett

The World Health Organization (WHO) is facing an unprecedented crisis that threatens its position as the premier international health agency. To ensure its leading role, it must rethink its internal governance and revamp its financing mechanisms.

Nature Medicine 18, 653 (2012). doi:10.1038/nm.2769

Author: Darwin J Prockop

A new study using a mouse model of lung diseases is the first demonstration in vivo that bone marrow–derived stromal cells can repair tissue injury through the transfer of mitochondria (pages 759–765). This suggests that rescue of injured cells through mitochondrial transfer may be an important process in many diseases.

Nature Medicine 18, 654 (2012). doi:10.1038/nm.2767

Authors: Namiko Hoshi & Ruslan Medzhitov

The normally harmless behavior of bacteria in the intestinal tract is maintained by community structure and the integrity of host defenses. When either or both of these are compromised, a few disgruntled outcasts can cause a riot, taking down the whole neighborhood (pages 799–806).

Nature Medicine 18, 656 (2012). doi:10.1038/nm.2773

Author: David E Cummings

Clinicians note that bariatric operations can dramatically resolve type 2 diabetes, often before and out of proportion to postoperative weight loss. Now two randomized controlled trials formally show superior results from surgical compared with medical diabetes care, including among only mildly obese patients. The concept of 'metabolic surgery' to treat diabetes has taken a big step forward.

Nature Medicine 18, 658 (2012). doi:10.1038/nm.2761

Authors: Jing Chen & Lois E H Smith

Age-related macular degeneration (AMD) is the most common cause of blindness in the elderly. AMD progression is associated with alterations in inflammatory pathways and the immune system. A new study identifies a protective role for inflammasomes in AMD, suggesting that inflammasome activation might be manipulated as a potential therapeutic strategy for this condition (pages 791–798).

Nature Medicine 18, 660 (2012). doi:10.1038/nm.2762

Authors: Wolfgang A Linke & Sandra Bücker

Alternative splicing ensures the expression of functionally diverse proteins from individual genes; however, aberrant mRNA splicing is associated with various conditions, including heart disease. A recent study provides new mechanistic insights into heart failure by showing that a human cardiomyopathy-linked mutation in a cardiac splice factor affects post-transcriptional regulation, causing the expression of anomalous isoforms of a whole network of cardiac proteins (pages 766–773).

Nature Medicine 18, 662 (2012). doi:10.1038/nm.2765

Authors: André Kriegeskorte & Georg Peters

Mechanisms triggering methicillin-resistant Staphylococcus aureus (MRSA) epidemics are poorly understood. A recent study provides new evidence that horizontal gene transfer may be the culprit for the emergence of new resistant and virulent MRSA clones.

Nature Medicine 18, 666 (2012). doi:10.1038/nm.2747

Authors: Rachel Larder & Stephen O'Rahilly

Losing weight can pose a challenge, but how to avoid putting those pounds back on can be a real struggle. A major health problem for obese people is that diseases linked to obesity, such as type 2 diabetes and cardiovascular disease, put their lives at risk, even in young individuals. Although bariatric surgery—a surgical method to reduce or modify the gastrointestinal tract—was originally envisioned for the most severe cases of obesity, evidence suggests that the benefit of this procedure may not be limited to the staggering weight loss it causes. Endogenous factors released from the gut, and modified after surgery, may explain why bariatric surgery can be beneficial for obesity-related diseases and why operated individuals successfully maintain the weight loss. In 'Bedside to Bench,' Rachel Larder and Stephen O'Rahilly peruse a human study with dieters who regained weight despite a successful diet. Appetite-regulating hormones in the gut may be responsible for this relapse in the long term. In 'Bench to Bedside,' Keval Chandarana and Rachel Batterham examine how two different methods of bariatric surgery highlight the relevance of gut-derived hormones not only in inducing sustained weight loss but also in improving glucose homeostasis. These insights may open new avenues to bypass the surgery and obtain the same results with targeted drugs.

Nature Medicine 18, 668 (2012). doi:10.1038/nm.2748

Authors: Keval Chandarana & Rachel L Batterham

Losing weight can pose a challenge, but how to avoid putting those pounds back on can be a real struggle. A major health problem for obese people is that diseases linked to obesity, such as type 2 diabetes and cardiovascular disease, put their lives at risk, even in young individuals. Although bariatric surgery—a surgical method to reduce or modify the gastrointestinal tract—was originally envisioned for the most severe cases of obesity, evidence suggests that the benefit of this procedure may not be limited to the staggering weight loss it causes. Endogenous factors released from the gut, and modified after surgery, may explain why bariatric surgery can be beneficial for obesity-related diseases and why operated individuals successfully maintain the weight loss. In 'Bedside to Bench,' Rachel Larder and Stephen O'Rahilly peruse a human study with dieters who regained weight despite a successful diet. Appetite-regulating hormones in the gut may be responsible for this relapse in the long term. In 'Bench to Bedside,' Keval Chandarana and Rachel Batterham examine how two different methods of bariatric surgery highlight the relevance of gut-derived hormones not only in inducing sustained weight loss but also in improving glucose homeostasis. These insights may open new avenues to bypass the surgery and obtain the same results with targeted drugs.

Nature Medicine 18, 673 (2012). doi:10.1038/nm.2731

Author: Stephen T Holgate

Nature Medicine 18, 684 (2012). doi:10.1038/nm.2737

Authors: Bart N Lambrecht & Hamida Hammad

Nature Medicine 18, 693 (2012). doi:10.1038/nm.2755

Authors: Stephen J Galli & Mindy Tsai

Nature Medicine 18, 705 (2012). doi:10.1038/nm.2760

Authors: Sabina A Islam & Andrew D Luster

Nature Medicine 18, 716 (2012). doi:10.1038/nm.2678

Author: Sally E Wenzel

Nature Medicine 18, 726 (2012). doi:10.1038/nm.2768

Authors: Patrick G Holt & Peter D Sly

Nature Medicine 18, 736 (2012). doi:10.1038/nm.2754

Author: Cezmi A Akdis

Nature Medicine 18, 751 (2012). doi:10.1038/nm.2735

Authors: Bryan C Petersen, Alison L Budelsky, Alan P Baptist, Matthew A Schaller & Nicholas W Lukacs

Nature Medicine 18, 759 (2012). doi:10.1038/nm.2736

Authors: Mohammad Naimul Islam, Shonit R Das, Memet T Emin, Michelle Wei, Li Sun, Kristin Westphalen, David J Rowlands, Sadiqa K Quadri, Sunita Bhattacharya & Jahar Bhattacharya

Nature Medicine 18, 766 (2012). doi:10.1038/nm.2693

Authors: Wei Guo, Sebastian Schafer, Marion L Greaser, Michael H Radke, Martin Liss, Thirupugal Govindarajan, Henrike Maatz, Herbert Schulz, Shijun Li, Amanda M Parrish, Vita Dauksaite, Padmanabhan Vakeel, Sabine Klaassen, Brenda Gerull, Ludwig Thierfelder, Vera Regitz-Zagrosek, Timothy A Hacker, Kurt W Saupe, G William Dec, Patrick T Ellinor, Calum A MacRae, Bastian Spallek, Robert Fischer, Andreas Perrot, Cemil Özcelik, Kathrin Saar, Norbert Hubner & Michael Gotthardt

Nature Medicine 18, 774 (2012). doi:10.1038/nm.2728

Authors: Tobias Eckle, Katherine Hartmann, Stephanie Bonney, Susan Reithel, Michel Mittelbronn, Lori A Walker, Brian D Lowes, Jun Han, Christoph H Borchers, Peter M Buttrick, Douglas J Kominsky, Sean P Colgan & Holger K Eltzschig

Nature Medicine 18, 783 (2012). doi:10.1038/nm.2709

Authors: Jiali Li, Jianmin Chen, Christopher L Ricupero, Ronald P Hart, Melanie S Schwartz, Alexander Kusnecov & Karl Herrup

Nature Medicine 18, 791 (2012). doi:10.1038/nm.2717

Authors: Sarah L Doyle, Matthew Campbell, Ema Ozaki, Robert G Salomon, Andres Mori, Paul F Kenna, Gwyneth Jane Farrar, Anna-Sophia Kiang, Marian M Humphries, Ed C Lavelle, Luke A J O'Neill, Joe G Hollyfield & Peter Humphries

Nature Medicine 18, 799 (2012). doi:10.1038/nm.2729

Authors: Janelle S Ayres, Norver J Trinidad & Russell E Vance

Nature Medicine 18, 807 (2012). doi:10.1038/nm.2700

Authors: Elena Provasi, Pietro Genovese, Angelo Lombardo, Zulma Magnani, Pei-Qi Liu, Andreas Reik, Victoria Chu, David E Paschon, Lei Zhang, Jurgen Kuball, Barbara Camisa, Attilio Bondanza, Giulia Casorati, Maurilio Ponzoni, Fabio Ciceri, Claudio Bordignon, Philip D Greenberg, Michael C Holmes, Philip D Gregory, Luigi Naldini & Chiara Bonini

Nature Medicine 18, 816 (2012). doi:10.1038/nm.2692

Authors: Min Li, Xin Du, Amer E Villaruz, Binh An Diep, Decheng Wang, Yan Song, Yueru Tian, Jinhui Hu, Fangyou Yu, Yuan Lu & Michael Otto

The molecular processes underlying epidemic waves of methicillin-resistant Staphylococcus aureus (MRSA) infection are poorly understood. Although a major role has been attributed to the acquisition of virulence determinants by horizontal gene transfer, there are insufficient epidemiological and functional data supporting that concept. We here report the spread of clones containing a previously extremely rare mobile genetic element–encoded gene, sasX. We demonstrate that sasX has a key role in MRSA colonization and pathogenesis, substantially enhancing nasal colonization, lung disease and abscess formation and promoting mechanisms of immune evasion. Moreover, we observed the recent spread of sasX from sequence type 239 (ST239) to invasive clones belonging to other sequence types. Our study identifies sasX as a quickly spreading crucial determinant of MRSA pathogenic success and a promising target for therapeutic interference. Our results provide proof of principle that horizontal gene transfer of key virulence determinants drives MRSA epidemic waves.

Nature Medicine 18, 820 (2012). doi:10.1038/nm.2724

Authors: Rebecca L Leshan, Megan Greenwald-Yarnell, Christa M Patterson, Ian E Gonzalez & Martin G Myers

Few effective measures exist to combat the worldwide obesity epidemic, and the identification of potential therapeutic targets requires a deeper understanding of the mechanisms that control energy balance. Leptin, an adipocyte-derived hormone that signals the long-term status of bodily energy stores, acts through multiple types of leptin receptor long isoform (LepRb)-expressing neurons (called here LepRb neurons) in the brain to control feeding, energy expenditure and endocrine function. The modest contributions to energy balance that are attributable to leptin action in many LepRb populations suggest that other previously unidentified hypothalamic LepRb neurons have key roles in energy balance. Here we examine the role of LepRb in neuronal nitric oxide synthase (NOS1)-expressing LebRb (LepRbNOS1) neurons that comprise approximately 20% of the total hypothalamic LepRb neurons. Nos1cre-mediated genetic ablation of LepRb (LeprNos1KO) in mice produces hyperphagic obesity, decreased energy expenditure and hyperglycemia approaching that seen in whole-body LepRb-null mice. In contrast, the endocrine functions in LeprNos1KO mice are only modestly affected by the genetic ablation of LepRb in these neurons. Thus, hypothalamic LepRbNOS1 neurons are a key site of action of the leptin-mediated control of systemic energy balance.

Nature Medicine 18, 824 (2012). doi:10.1038/nm.2720

Authors: Katherina Siewert, Joachim Malotka, Naoto Kawakami, Hartmut Wekerle, Reinhard Hohlfeld & Klaus Dornmair

Nature Medicine 18, 829 (2012). doi:10.1038/nm.2721

Authors: Moritz F Kircher, Adam de la Zerda, Jesse V Jokerst, Cristina L Zavaleta, Paul J Kempen, Erik Mittra, Ken Pitter, Ruimin Huang, Carl Campos, Frezghi Habte, Robert Sinclair, Cameron W Brennan, Ingo K Mellinghoff, Eric C Holland & Sanjiv S Gambhir