Agonists of Orally Expressed TRP Channels Stimulate Salivary Secretion and Modify the Salivary Proteome.

Natural compounds that can stimulate salivary secretion are of interest in developing treatments for xerostomia, the perception of a dry mouth, that affects between 10 and 30% of the adult and elderly population. Chemesthetic transient receptor potential (TRP) channels are expressed in the surface of the oral mucosa. The TRPV1 agonists capsaicin and piperine have been shown to increase salivary flow when introduced into the oral cavity but the sialogogic properties of other TRP channel agonists have not been investigated. In this study we have determined the influence of different TRP channel agonists on the flow and protein composition of saliva. Mouth rinsing with the TRPV1 agonist nonivamide or menthol, a TRPM8 agonist, increased whole mouth saliva (WMS) flow and total protein secretion compared with unstimulated saliva, the vehicle control mouth rinse or cinnamaldehyde, a TRPA1 agonist. Nonivamide also increased the flow of labial minor gland saliva but parotid saliva flow rate was not increased. The influence of TRP channel agonists on the composition and function of the salivary proteome was investigated using a multi-batch quantitative MS method novel to salivary proteomics. Inter-personal and inter-mouth rinse variation was observed in the secreted proteomes and, using a novel bioinformatics method, inter-day variation was identified with some of the mouth rinses. Significant changes in specific salivary proteins were identified after all mouth rinses. In the case of nonivamide, these changes were attributed to functional shifts in the WMS secreted, primarily the over representation of salivary and nonsalivary cystatins which was confirmed by immunoassay. This study provides new evidence of the impact of TRP channel agonists on the salivary proteome and the stimulation of salivary secretion by a TRPM8 channel agonist, which suggests that TRP channel agonists are potential candidates for developing treatments for sufferers of xerostomia.

Differences in the Natural Enamel Surface and Acquired Enamel Pellicle following Exposure to Citric or Hydrochloric Acid.

OBJECTIVES: The aim of this study was to investigate variations in the interaction between enamel, that is, the acquired enamel pellicle (AEP) and citric or hydrochloric acid. MATERIALS AND METHODS: A 24-h AEP was formed on natural enamel specimens (n = 40) from pooled whole mouth human saliva. Samples were randomly allocated to citric (0.3%, pH 3.2) or hydrochloric (HCl) acid (0.01 M, pH 2.38) exposure for 30 or 300 s. The total protein concentration (TPC), and phosphorous and calcium concentrations of the pellicle were determined before and after acid exposure, and again after re-immersion in saliva. Surface roughness and tandem scanning confocal microscopy imaging were used to assess enamel changes. RESULTS: After 300 s of citric acid exposure, the mean ± SD TPC reduced from 5.1 ± 1.1 to 3.5 ± 1.1 mg/mL (p < 0.05). In contrast, after 300 s of HCl exposure, the mean TPC did not reduce significantly from baseline (6.6 ± 1.1 to 5.7 ± 0.7 mg/mL) but was significantly reduced in the reformed pellicle to 4.9 ± 1.2 mg/mL (p < 0.001). This reduction occurred after significant release of calcium and phosphorous from the enamel surface (p < 0.001). Thirty seconds of exposure to either acid had no obvious effect on the AEP. The surface roughness of the enamel decreased after acid exposure but no differences between groups was observed. CONCLUSIONS: These findings indicate that citric acid interacted with proteins in the AEP upon contact, offering enamel protection. In contrast, HCl appeared to bypass the pellicle, and reduced protein was observed only after changes in the enamel chemical composition.

Efficacy of the cardiac septal occluder in the treatment of post-bariatric surgery leaks and fistulas.

BACKGROUND: Endoscopy has evolved to become first-line therapy for the treatment of post-bariatric leaks; however, many sessions are often required with variable success rates. Due to these limitations, the use of the cardiac septal defect occluder (CSDO) has recently been reported in this population. METHODS: The study population was a multicenter retrospective series of patients with post-bariatric surgical leaks who underwent treatment with CSDO placement. Data on the type of surgery, previous treatment details, fistula dimensions, success rate, and adverse events were collected. Leaks were grouped according to the International Sleeve Gastrectomy Expert Panel Consensus. Outcomes included technical and clinical success and safety of the CSDO. Regression analysis was performed to determine the predictors of response. RESULTS: Forty-three patients with leaks were included (31 sleeve gastrectomy and 12 Roux-en-Y gastric bypass). They were divided into acute (n = 3), early (n = 5), late (n = 23), and chronic (n = 12). Forty patients had failed previous endoscopic treatment and 3 patients had CSDO as the primary treatment. Median follow-up was 34 weeks. Technical success was achieved in all patients and clinical success in 39 patients (90.7%). All chronic, late, and early leaks were successfully closed, except one undrained late leak. The 5 patients with early leaks had an initial satisfactory response, but within 30 days, drainage recurred. The CSDOs were removed and replaced with larger-diameter devices leading to permanent defect closure. Acute leaks were not successfully closed in all 3 patients. Regression analysis showed that chronicity and previous treatment were associated with fistula closure; success rates for late/chronic leaks versus acute/early leaks were 97.1% and 62.5%, respectively (P = .0023). CONCLUSION: This observational study found that the CSDO had a high efficacy rate in patients with non-acute leaks, with no adverse events. All early, late, and chronic leaks were successfully closed, except for one undrained late leak. However, early leaks required a second placement of a larger CSDO in all cases. These results suggest that the CSDO should be considered for non-acute fistula and that traditional closure methods are likely preferred in the acute and early settings.

Results of a large-scale randomized behavior change intervention on road safety in Kenya.

Road accidents kill 1.3 million people each year, most in the developing world. We test the efficacy of evocative messages, delivered on stickers placed inside Kenyan matatus, or minibuses, in reducing road accidents. We randomize the intervention, which nudges passengers to complain to their drivers directly, across 12,000 vehicles and find that on average it reduces insurance claims rates of matatus by between one-quarter and one-third and is associated with 140 fewer road accidents per year than predicted. Messages promoting collective action are especially effective, and evocative images are an important motivator. Average maximum speeds and average moving speeds are 1-2 km/h lower in vehicles assigned to treatment. We cannot reject the null hypothesis of no placebo effect. We were unable to discern any impact of a complementary radio campaign on insurance claims. Finally, the sticker intervention is inexpensive: we estimate the cost-effectiveness of the most impactful stickers to be between $10 and $45 per disability-adjusted life-year saved.

Improving out-of-hours surgical patient care.

PURPOSE: The Royal College of Surgeons recognises patient handover as the point at which patients are collectively at their most vulnerable. Concerns were raised in a London teaching hospital surgical department regarding an unstructured handover system, poor access to relevant clinical information, and inadequate weekend staffing. A quality improvement programme was designed and implemented to respond to these concerns and improve patient safety. The paper aims to discuss these issues. DESIGN/METHODOLOGY/APPROACH: A structured questionnaire was distributed to staff and results used to construct a diagram outlining the main factors influencing weekend patient safety. This framework was used to design changes, including a new electronic handover tool, regular handover meetings and additional weekend staff. Regular staff training was provided, and success was assessed in a continuous audit cycle with the results fed back to team leaders. FINDINGS: Over a three-month period, the handover meeting recorded an attendance rate consistently above 80 per cent. The electronic handover entries were scored according to seven criteria (correct layout; key information, i.e.: patient location, clinical priority, active issues, resuscitation status, test results and weekend plan), averaging between 42.2 and 92.9 per cent, with progressive improvement seen over the assessment period. Weekend staffing was increased by 50 per cent, allowing a dedicated team to care for stable inpatients and to oversee discharges. ORIGINALITY/VALUE: This improvement programme delivered lasting and significant change in response to staff concerns. It resulted in a more structured and reliable weekend system and established key mechanisms for dynamic performance feedback.

Child diarrhoea and nutritional status in rural Rwanda: a cross-sectional study to explore contributing environmental and demographic factors.

OBJECTIVE: To explore associations of environmental and demographic factors with diarrhoea and nutritional status among children in Rusizi district, Rwanda. METHODS: We obtained cross-sectional data from 8847 households in May-August 2013 from a baseline survey conducted for an evaluation of an integrated health intervention. We collected data on diarrhoea, water quality, and environmental and demographic factors from households with children <5, and anthropometry from children <2. We conducted log-binomial regression using diarrhoea, stunting and wasting as dependent variables. RESULTS: Among children <5, 8.7% reported diarrhoea in the previous 7 days. Among children <2, stunting prevalence was 34.9% and wasting prevalence was 2.1%. Drinking water treatment (any method) was inversely associated with caregiver-reported diarrhoea in the previous 7 days (PR = 0.79, 95% CI: 0.68-0.91). Improved source of drinking water (PR = 0.80, 95% CI: 0.73-0.87), appropriate treatment of drinking water (PR = 0.88, 95% CI: 0.80-0.96), improved sanitation facility (PR = 0.90, 95% CI: 0.82-0.97), and complete structure (having walls, floor and roof) of the sanitation facility (PR = 0.65, 95% CI: 0.50-0.84) were inversely associated with stunting. None of the exposure variables were associated with wasting. A microbiological indicator of water quality was not associated with diarrhoea or stunting. CONCLUSIONS: Our findings suggest that in Rusizi district, appropriate treatment of drinking water may be an important factor in diarrhoea in children <5, while improved source and appropriate treatment of drinking water as well as improved type and structure of sanitation facility may be important for linear growth in children <2. We did not detect an association with water quality.

Documenting the birth of a financial economy.

The birth and explosive growth of mobile money in Kenya has provided economists with an opportunity to study the evolution and impact of a new financial system. Mobile money is an innovation that allows individuals to store, send, and receive money on their mobile phone via text message. This system has opened up basic financial services to many who were previously excluded, and has had real and measurable impacts on the ability of households to protect themselves against health risks. Using a unique survey instrument covering nearly 2,300 households over 2008-2010, we first document the lightning-fast adoption of mobile money in Kenya, which was faster than most documented modern technologies in the United States. We then present evidence on how this innovation allows households to respond better to unexpected adverse health events. We find that in the face of these events, users of mobile money are better able to tap into remittances to finance additional health care costs without having to forego necessary expenditures on education, food, and other consumption needs.

Polbase: a repository of biochemical, genetic and structural information about DNA polymerases.

Polbase (http://polbase.neb.com) is a freely accessible database of DNA polymerases and related references. It has been developed in a collaborative model with experts whose contributions reflect their varied backgrounds in genetics, structural biology and biochemistry. Polbase is designed to compile detailed results of polymerase experimentation, presenting them in a dynamic view to inform further research. After validation, results from references are displayed in context with relevant experimental details and are always traceable to their source publication. Polbase is connected to other resources, including PubMed, UniProt and the RCSB Protein Data Bank, to provide multi-faceted views of polymerase knowledge. In addition to a simple web interface, Polbase data is exposed for custom analysis by external software. With the contributions of many polymerase investigators, Polbase has become a powerful research tool covering most important aspects of polymerases, from sequence and structure to biochemistry.

Rapid incorporation kinetics and improved fidelity of a novel class of 3'-OH unblocked reversible terminators.

Recent developments of unique nucleotide probes have expanded our understanding of DNA polymerase function, providing many benefits to techniques involving next-generation sequencing (NGS) technologies. The cyclic reversible termination (CRT) method depends on efficient base-selective incorporation of reversible terminators by DNA polymerases. Most terminators are designed with 3'-O-blocking groups but are incorporated with low efficiency and fidelity. We have developed a novel class of 3'-OH unblocked nucleotides, called Lightning Terminators™, which have a terminating 2-nitrobenzyl moiety attached to hydroxymethylated nucleobases. A key structural feature of this photocleavable group displays a 'molecular tuning' effect with respect to single-base termination and improved nucleotide fidelity. Using Therminator DNA polymerase, we demonstrate that these 3'-OH unblocked terminators exhibit superior enzymatic performance compared to two other reversible terminators, 3'-O-amino-TTP and 3'-O-azidomethyl-TTP. Lightning Terminators show maximum incorporation rates (k(pol)) that range from 35 to 45 nt/s, comparable to the fastest NGS chemistries, yet with catalytic efficiencies (k(pol)/K(D)) comparable to natural nucleotides. Pre-steady-state kinetic studies of thymidine analogs revealed that the major determinant for improved nucleotide selectivity is a significant reduction in k(pol) by >1000-fold over TTP misincorporation. These studies highlight the importance of structure-function relationships of modified nucleotides in dictating polymerase performance.

Interactions and pattern formation in a macroscopic magnetocapillary SALR system of mermaid cereal.

When particles are deposited at a fluid interface they tend to aggregate by capillary attraction to minimize the overall potential energy of the system. In this work, we embed floating millimetric disks with permanent magnets to introduce a competing repulsion effect and study their pattern formation in equilibrium. The pairwise energy landscape of two disks is described by a short-range attraction and long-range repulsion (SALR) interaction potential, previously documented in a number of microscopic condensed matter systems. Such competing interactions enable a variety of pairwise equilibrium states, including the possibility of a local minimum energy corresponding to a finite disk spacing. Two-dimensional (2D) experiments and simulations in confined geometries demonstrate that as the areal packing fraction is increased, the dilute repulsion-dominated lattice state becomes unstable to the spontaneous formation of localized clusters, which eventually merge into a system-spanning striped pattern. Finally, we demonstrate that the equilibrium pattern can be externally manipulated by the application of a supplemental vertical magnetic force that remotely enhances the effective capillary attraction.

The COVID-19 ambulance response assessment (CARA) study: a national survey of ambulance service healthcare professionals' preparedness and response to the COVID-19 pandemic.

Background: The COVID-19 pandemic placed significant demand on the NHS, including ambulance services, but it is unclear how this affected ambulance service staff and paramedics in other clinical settings (e.g. urgent and primary care, armed services, prisons). This study aimed to measure the self-perceived preparedness and impact of the first wave of the pandemic on paramedics' psychological stress and perceived ability to deliver care. Methods: Ambulance clinicians and paramedics working in other healthcare settings were invited to participate in a three-phase sequential online survey during the acceleration (April 2020), peak (May 2020) and deceleration (September/October 2020) phases of the first wave of COVID-19 in the United Kingdom. Recruitment used social media, Trust internal bulletins and the College of Paramedics' communication channels, employing a convenience sampling strategy. Data were collected using purposively developed open- and closed-ended questions and the validated general health questionnaire-12 (GHQ-12). Data were analysed using multi-level linear and logistic regression models. Results: Phase 1 recruited 3717 participants, reducing to 2709 (73%) by phase 2 and 2159 (58%) by phase 3. Participants were mostly male (58%, n = 2148) and registered paramedics (n = 1992, 54%). Mean (standard deviation) GHQ-12 scores were 16.5 (5.2) during phase 1, reducing to 15.2 (6.7) by phase 3. A total of 84% of participants (n = 3112) had a GHQ-12 score ≥ 12 during the first phase, indicating psychological distress. Participants that had higher GHQ-12 scores were feeling unprepared for the pandemic, and reported a lack of confidence in using personal protective equipment and managing cardiac arrests in confirmed or suspected COVID-19 patients. Conclusions: Most participants reported psychological distress, the reasons for which are multi-factorial. Ambulance managers need to be aware of the risks to staff mental health and take action to mitigate these, to support staff in the delivery of unscheduled, emergency and urgent care under these additional pressures.

Interventional management of malignant bone tumours.

In the last few decades, interventional radiology (IR) has significantly increased its role in the management of bone tumours including bone metastases (BM) that represent the most common type of tumour involving the bone. The current IR management of BM is based on the 'palliative-curative' paradigm and relies on the use of consolidative (i.e. osteplasty, osteosynthesis) and/or ablation (i.e. cryoablation, radiofrequency ablation, electrochemotherapy) techniques. The present narrative review will overview the current role of IR for the management of BM.

Patient satisfaction with telephone consultations in cardiology outpatients during the COVID-19 pandemic.

The COVID-19 pandemic required a radical change in healthcare delivery methods, including the remote delivery of many outpatient services. We aimed to understand patient satisfaction with telephone consultations. Patients who had undergone a cardiology telephone consultation between 24 February and 19 July 2021 were asked to complete a survey. The survey assessed their satisfaction with the consultation and their preference between remote and face-to-face consultation. The 56 responses demonstrated high levels of satisfaction with 56% agreeing they were "completely satisfied" with the consultation compared with 5% who disagreed. However, 63% would have preferred a face-to-face appointment compared with 22% preferring a telephone consultation. No patterns were observed that might help to guide who should be offered the different modalities of consultation; to maximise patient satisfaction a flexible and individualised approach is likely to be required.

Development and implementation of a simple and rapid extraction-free saliva SARS-CoV-2 RT-LAMP workflow for workplace surveillance.

Effective management of the COVID-19 pandemic requires widespread and frequent testing of the population for SARS-CoV-2 infection. Saliva has emerged as an attractive alternative to nasopharyngeal samples for surveillance testing as it does not require specialized personnel or materials for its collection and can be easily provided by the patient. We have developed a simple, fast, and sensitive saliva-based testing workflow that requires minimal sample treatment and equipment. After sample inactivation, RNA is quickly released and stabilized in an optimized buffer, followed by reverse transcription loop-mediated isothermal amplification (RT-LAMP) and detection of positive samples using a colorimetric and/or fluorescent readout. The workflow was optimized using 1,670 negative samples collected from 172 different individuals over the course of 6 months. Each sample was spiked with 50 copies/µL of inactivated SARS-CoV-2 virus to monitor the efficiency of viral detection. Using pre-defined clinical samples, the test was determined to be 100% specific and 97% sensitive, with a limit of detection of 39 copies/mL. The method was successfully implemented in a CLIA laboratory setting for workplace surveillance and reporting. From April 2021-February 2022, more than 30,000 self-collected samples from 755 individuals were tested and 85 employees tested positive mainly during December and January, consistent with high infection rates in Massachusetts and nationwide.

Effects of a mobile phone short message service on antiretroviral treatment adherence in Kenya (WelTel Kenya1): a randomised trial.

BACKGROUND: Mobile (cell) phone communication has been suggested as a method to improve delivery of health services. However, data on the effects of mobile health technology on patient outcomes in resource-limited settings are limited. We aimed to assess whether mobile phone communication between health-care workers and patients starting antiretroviral therapy in Kenya improved drug adherence and suppression of plasma HIV-1 RNA load. METHODS: WelTel Kenya1 was a multisite randomised clinical trial of HIV-infected adults initiating antiretroviral therapy (ART) in three clinics in Kenya. Patients were randomised (1:1) by simple randomisation with a random number generating program to a mobile phone short message service (SMS) intervention or standard care. Patients in the intervention group received weekly SMS messages from a clinic nurse and were required to respond within 48 h. Randomisation, laboratory assays, and analyses were done by investigators masked to treatment allocation; however, study participants and clinic staff were not masked to treatment. Primary outcomes were self-reported ART adherence (>95% of prescribed doses in the past 30 days at both 6 and 12 month follow-up visits) and plasma HIV-1 viral RNA load suppression (<400 copies per mL) at 12 months. The primary analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT00830622. FINDINGS: Between May, 2007, and October, 2008, we randomly assigned 538 participants to the SMS intervention (n=273) or to standard care (n=265). Adherence to ART was reported in 168 of 273 patients receiving the SMS intervention compared with 132 of 265 in the control group (relative risk [RR] for non-adherence 0·81, 95% CI 0·69-0·94; p=0·006). Suppressed viral loads were reported in 156 of 273 patients in the SMS group and 128 of 265 in the control group, (RR for virologic failure 0·84, 95% CI 0·71-0·99; p=0·04). The number needed to treat (NNT) to achieve greater than 95% adherence was nine (95% CI 5·0-29·5) and the NNT to achieve viral load suppression was 11 (5·8-227·3). INTERPRETATION: Patients who received SMS support had significantly improved ART adherence and rates of viral suppression compared with the control individuals. Mobile phones might be effective tools to improve patient outcome in resource-limited settings. FUNDING: US President's Emergency Plan for AIDS Relief.

Characterization of Sulfolobus islandicus rod-shaped virus 2 gp19, a single-strand specific endonuclease.

The hyperthermophilic Sulfolobus islandicus rod-shaped virus 2 (SIRV2) encodes a 25-kDa protein (SIRV2gp19) annotated as a hypothetical protein with sequence homology to the RecB nuclease superfamily. Even though SIRV2gp19 homologs are conserved throughout the rudivirus family and presumably play a role in the viral life cycle, SIRV2gp19 has not been functionally characterized. To define the minimal requirements for activity, SIRV2gp19 was purified and tested under varying conditions. SIRV2gp19 is a single-strand specific endonuclease that requires Mg(2+) for activity and is inactive on double-stranded DNA. A conserved aspartic acid in RecB nuclease superfamily Motif II (D89) is also essential for SIRV2gp19 activity and mutation to alanine (D89A) abolishes activity. Therefore, the SIRV2gp19 cleavage mechanism is similar to previously described RecB nucleases. Finally, SIRV2gp19 single-stranded DNA endonuclease activity could play a role in host chromosome degradation during SIRV2 lytic infection.

A survey of ambulance clinicians' perceptions of recording and communicating patient information electronically.

OBJECTIVE: Ambulance services are evolving from use of paper-based recording of patient information to electronic platforms and the impact of this change has yet to be fully explored. The aim of this study is to explore how the introduction of a system permitting electronic information capture and its subsequent sharing were perceived by the ambulance clinicians using it. METHODS: An online questionnaire was designed based upon the technology acceptance model and distributed throughout one ambulance service in the south east of England. Closed-ended questions with Likert scales were used to collect data from patient-facing staff who use an online community falls and diabetic referral platform or an electronic messaging system to update GPs following a patient encounter. RESULTS: There were 273 responses from ambulance clinicians. Most participants agreed that they used tablet computers and smartphones to make their life easier (85% and 86%, respectively). Most participants felt that referring patients to a community falls or diabetic team electronically was an efficient use of their time (81% and 81%, respectively) and many believed that these systems improved the communication of confidential patient information. GP summaries were perceived as increasing time spent on scene but most participants (89%) believed they enabled collaborative working. Overall, collecting and sharing patient information electronically was perceived by most participants as beneficial to their practice. CONCLUSION: In this study, the ability to electronically refer patients to community services and share patient encounters with the GP was predominantly perceived as both safe for patients and an effective use of the participants' clinical time. However, there is often still a need to communicate to GPs in real time, demonstrating that technology could complement, rather than replace, how clinicians communicate.

Ready-to-use nanopore platform for the detection of any DNA/RNA oligo at attomole range using an Osmium tagged complementary probe.

Nanopores can serve as single molecule sensors. We exploited the MinION, a portable nanopore device from Oxford Nanopore Technologies, and repurposed it to detect any DNA/RNA oligo (target) in a complex mixture by conducting voltage-driven ion-channel measurements. The detection and quantitation of the target is enabled by the use of a unique complementary probe. Using a validated labeling technology, probes are tagged with a bulky Osmium tag (Osmium tetroxide 2,2'-bipyridine), in a way that preserves strong hybridization between probe and target. Intact oligos traverse the MinION's nanopore relatively quickly compared to the device's acquisition rate, and exhibit count of events comparable to the baseline. Counts are reported by a publicly available software, OsBp_detect. Due to the presence of the bulky Osmium tag, probes traverse more slowly, produce multiple counts over the baseline, and are even detected at single digit attomole (amole) range. In the presence of the target the probe is "silenced". Silencing is attributed to a 1:1 double stranded (ds) complex that does not fit and cannot traverse this nanopore. This ready-to-use platform can be tailored as a diagnostic test to meet the requirements for point-of-care cell-free tumor DNA (ctDNA) and microRNA (miRNA) detection and quantitation in body fluids.

A catalogue of biochemically diverse CRISPR-Cas9 orthologs.

Bacterial Cas9 nucleases from type II CRISPR-Cas antiviral defence systems have been repurposed as genome editing tools. Although these proteins are found in many microbes, only a handful of variants are used for these applications. Here, we use bioinformatic and biochemical analyses to explore this largely uncharacterized diversity. We apply cell-free biochemical screens to assess the protospacer adjacent motif (PAM) and guide RNA (gRNA) requirements of 79 Cas9 proteins, thus identifying at least 7 distinct gRNA classes and 50 different PAM sequence requirements. PAM recognition spans the entire spectrum of T-, A-, C-, and G-rich nucleotides, from single nucleotide recognition to sequence strings longer than 4 nucleotides. Characterization of a subset of Cas9 orthologs using purified components reveals additional biochemical diversity, including both narrow and broad ranges of temperature dependence, staggered-end DNA target cleavage, and a requirement for long stretches of homology between gRNA and DNA target. Our results expand the available toolset of RNA-programmable CRISPR-associated nucleases.

How do Self-Assembling Antimicrobial Lipopeptides Kill Bacteria?

Antimicrobial peptides are promising alternatives to traditional antibiotics. A group of self-assembling lipopeptides was formed by attaching an acyl chain to the N-terminus of α-helix-forming peptides with the sequence Cx-G(IIKK)yI-NH2 (CxGy, x = 4-12 and y = 2). CxGy self-assemble into nanofibers above their critical aggregation concentrations (CACs). With increasing x, the CACs decrease and the hydrophobic interactions increase, promoting secondary structure transitions within the nanofibers. Antimicrobial activity, determined by the minimum inhibition concentration (MIC), also decreases with increasing x, but the MICs are significantly smaller than the CACs, suggesting effective bacterial membrane-disrupting power. Unlike conventional antibiotics, both C8G2 and C12G2 can kill Staphylococcus aureus and Escherichia coli after only minutes of exposure under the concentrations studied. C12G2 nanofibers have considerably faster killing dynamics and lower cytotoxicity than their nonaggregated monomers. Antimicrobial activity of peptide aggregates has, to date, been underexploited, and it is found to be a very promising mechanism for peptide design. Detailed evidence for the molecular mechanisms involved is provided, based on superresolution fluorescence microscopy, solid-state nuclear magnetic resonance, atomic force microscopy, neutron scattering/reflectivity, circular dichroism, and Brewster angle microscopy.