Syntaxin 4 is essential for hearing in human and zebrafish.

Congenital hearing impairment (HI) is a genetically highly heterogeneous disorder in which prompt recognition and intervention are crucial to optimize outcomes. In this study, we used exome sequencing to investigate a large consanguineous Pakistani family with eight affected individuals showing bilateral severe-to-profound HI. This identified a homozygous splice region variant in STX4 (c.232 + 6T>C), which causes exon skipping and a frameshift, that segregated with HI (two-point logarithm of odds (LOD) score = 5.9). STX4, a member of the syntaxin family, is a component of the SNARE machinery involved in several vesicle transport and recycling pathways. In silico analysis showed that murine orthologue Stx4a is highly and widespread expressed in the developing and adult inner ear. Immunofluorescent imaging revealed localization of STX4A in the cell body, cell membrane and stereocilia of inner and outer hair cells. Furthermore, a morpholino-based knockdown of stx4 in zebrafish showed an abnormal startle response, morphological and developmental defects, and a disrupted mechanotransduction function in neuromast hair cells measured via FM1-43 uptake. Our findings indicate that STX4 dysfunction leads to HI in humans and zebrafish and supports the evolutionary conserved role of STX4 in inner ear development and hair cell functioning.

Solving the fouling mechanisms in composite membranes for water purification: An advance approach.

With the increasing population worldwide more wastewater is created by human activities and discharged into the waterbodies. This is causing the contamination of aquatic bodies, thus disturbing the marine ecosystems. The rising population is also posing a challenge to meet the demands of fresh drinking water in the water-scarce regions of the world, where drinking water is made available to people by desalination process. The fouling of composite membranes remains a major challenge in water desalination. In this innovative study, we present a novel probabilistic approach to analyse and anticipate the predominant fouling mechanisms in the filtration process. Our establishment of a robust theoretical framework hinges upon the utilization of both the geometric law and the Hermia model, elucidating the concept of resistance in series (RIS). By manipulating the transmembrane pressure, we demonstrate effective management of permeate flux rate and overall product quality. Our investigations reveal a decrease in permeate flux in three distinct phases over time, with the final stage marked by a significant reduction due to the accumulation of a denser cake layer. Additionally, an increase in transmembrane pressure leads to a correlative rise in permeate flux, while also exerting negative effects such as membrane ruptures. Our study highlights the minimal immediate impact of the intermediate blocking mechanism (n = 1) on permeate flux, necessitating continuous monitoring for potential long-term effects. Additionally, we note a reduced membrane selectivity across all three fouling types (n = 0, n = 1.5, n = 2). Ultimately, our findings indicate that the membrane undergoes complete fouling with a probability of P = 0.9 in the presence of all three fouling mechanisms. This situation renders the membrane unable to produce water at its previous flow rate, resulting in a significant reduction in the desalination plant's productivity. I have demonstrated that higher pressure values notably correlate with increased permeate flux across all four membrane types. This correlation highlights the significant role of TMP in enhancing the production rate of purified water or desired substances through membrane filtration systems. Our innovative approach opens new perspectives for water desalination management and optimization, providing crucial insights into fouling mechanisms and proposing potential strategies to address associated challenges.

Achieving zero emission targets: The influence of green bonds on clean energy investment and environmental quality.

The effectiveness of green finance in driving clean energy and environmental sustainability in the current era is receiving attention. Therefore, this study proposes an empirical framework highlighting the effects of green bonds (GB) on clean energy investment (CEI), clean energy investment efficiency (CEE) and environmental sustainability of 29 green bond issuing countries between 2014 and 2022. Using system and difference GMM approaches, this study finds that (i) green bond issuance drives clean energy investment. (ii) Green bonds sufficiently enhance the selected countries' environmental quality. These results supplement the promotion of green bonds in increasing the transfer of funds towards renewable energy projects by reducing reliance on fossil fuels. (iii) Using Driscoll & Kraay, Fully Modified-OLS, and changing the dependent variable, this study further supported the idea that green bonds effectively promote the CEE and environmental sustainability of the chosen countries. (iv) Similarly, this study conducted income heterogeneity, showing that green bonds improve high- and middle-income countries' CEI and environmental quality. (v) Finally, the results indicate that resource consumption escalates CO2 emissions by declining the CEI. Technological innovations increase CEI, whereas they do not mitigate CO2 emissions directly, hinting at the requirement for a comprehensive approach. Therefore, inclusive policies on green bond frameworks, robust incentives, and rigorous environmental criteria should be implemented to attract investment in clean energy development and ensure the environmental sustainability of the selected countries.

Expansion of the Analytical Modeling of Capacitance for 1-N-1 Multilayered CID Structures with Monotonically Increasing/Decreasing Permittivity.

Capacitive sensors that utilize the Coplanar Interdigitated (CID) electrode structure are widely employed in various technical and analytical domains, such as healthcare, infectious disease management, pharmaceuticals, metrology, and environmental monitoring. The present exigency for lab-on-a-chip contrivances and the requisite for the miniaturization of sensors have led to the widespread adoption of CID sensors featuring multiple dielectric layers (DLs), either in the form of substrates or superstrates. Previously, we derived an analytical model for the capacitance of CID capacitive sensors with four distinct 1-N-1 patterns (namely, 1-1-1, 1-3-1, 1-5-1, and 1-11-1) using partial capacitance (PC) and conformal mapping (CM) techniques. The aforementioned model has been employed in various applications wherein the permittivity of successive layers exhibits a monotonic decrease as one moves away from the electrode plane, resulting in highly satisfactory outcomes. Nevertheless, the PC technique is inadequate for structures with multiple layers where the permittivity exhibits a monotonic increase as the distance from the electrodes increases. Given these circumstances, it is necessary to adapt the initial PC method to incorporate these novel configurations. In this work, we have discussed a new approach, splitting the concept of PC into partial parallel capacitance (PPC) and partial serial capacitance (PSC), where new CM transformations are proposed for the latter case. Thus, the present study proposes a novel methodology to expand upon our prior analytical framework, which aims to incorporate scenarios where the permittivity experiences a reduction across successive layers. The outcomes are juxtaposed with the finite element simulation and analytical findings.

Preventable morbidities of a successful intervention, Textiloma/Gossypiboma: A case series.

Preventable morbidities are serious conditions that have the potential to cause serious harm or death of the patient. One of the preventable morbidities is Gossypiboma or involuntary leaving of surgical sponge inside the body. The implication for the patient and the surgeon is grave. Gossypiboma is preventable if guidance and safety recommendations are followed. The purpose of presenting this case series is to rekindle awareness of the phenomena of Gossypiboma, highlight the implications, and stress prevention. Data of patients presented in the Lahore General Hospital was collected, which includes their demographic, clinical features, and management outcome. Their age, gender, surgery conducted, onset of symptoms, and salvage procedure were noted. Five cases are included in this case series from which it was concluded that Gossypiboma is encountered most commonly after intra-abdominal operation. Women are at increased risk during obstetric and gynaecological operations, though both genders are affected.

Respect and reflexivity: international education partnerships in primary care.

The UK general practice model has been described as the 'jewel in the crown' of the National Health Service and is widely respected and emulated around the world. In recent years, there has been a particular interest in the UK approach to primary care medical education, including at undergraduate and postgraduate levels, leading to a number of international education partnerships designed to draw on the best of UK experience and expertise in this area. Drawing on the limited academic literature in this area, and the authors' personal experiences of working across many international partnership projects with countries around the world, this article reflects on the central importance of respect and reflexivity when engaging in such work. A respectful approach relies on a genuine and deep curiosity for the local context, and a desire to empower partners to build their own solutions that are contextually authentic. A reflexive approach, meanwhile, relies on those engaging in partnerships to understand themselves as 'invited guests' and to remain mindful of current and historical power differentials and inequities when framing their engagement, looking both inwardly and outwardly as they conduct themselves. As primary care education around the world develops and expands, there may be a greater role for international partnerships and it is critically important that those engaging in such partnerships bring a thoughtful and scholarly lens to this work.

The interaction mechanisms of co-existing polybrominated diphenyl ethers and engineered nanoparticles in environmental waters: A critical review.

This review focuses on the occurrence and interactions of engineered nanoparticles (ENPs) and brominated flame retardants (BFRs) such as polybrominated diphenyl ethers (PBDEs) in water systems and the generation of highly complex compounds in the environment. The release of ENPs and BFRs (e.g. PBDEs) to aquatic environments during their usage and disposal are summarised together with their key interaction mechanisms. The major interaction mechanisms including electrostatic, van der Waals, hydrophobic, molecular bridging and steric, hydrogen and π-bonding, cation bridging and ligand exchange were identified. The presence of ENPs could influence the fate and behaviour of PBDEs through the interactions as well as induced reactions under certain conditions which increases the formation of complex compounds. The interaction leads to alteration of behaviour for PBDEs and their toxic effects to ecological receptors. The intermingled compound (ENPs-BFRs) would show different behaviour from the parental ENPs or BFRs, which are currently lack of investigation. This review provided insights on the interactions of ENPs and BFRs in artificial, environmental water systems and wastewater treatment plants (WWTPs), which are important for a comprehensive risk assessment.

Characterization and survival of broad-spectrum biocontrol agents against phytopathogenic fungi.

The current study intended to isolate, characterize and identify biocontrol bacteria possessing broad-spectrum antifungal activity from the phyllosphere of different crops including maize, wheat and potato and to assess their growth-promoting activity. In this study 14/113 biocontrol bacteria showed antifungal activity. Bacterial isolates M11 and M33 from maize out of 113 were re-selected on the basis of their strong (more than 50%) broad spectrum antifungal activity after their assessment against four economically important phytopathogenic fungi including Alternaria alternata, Rhizoctonia solani, Fusarium oxysporum and Fusarium verticillioides. The isolates were further assessed for plant growth promoting traits, i.e., indole-3-acetic acid production, phosphate solubilization, production of cellulase, microbial volatile compounds, hydrogen cyanide and siderophores. All fourteen isolates showed positive results for the production of indole-3-acetic acid hormone and cellulase enzyme, 10 isolates were positive for hydrogen cyanide production; siderophores production was observed in 7 isolates while 5 isolates showed ability to solubilize inorganic phosphate. Microbial volatile compounds were only synthesized by M11 and M33, which were identified as Bacillus amyloliquefaciens and Bacillus subtilis respectively by 16S rRNA gene sequencing. The survival study revealed that biocontrol bacteria B. amyloliquefaciens and B. subtilis have the ability to survive in cost effective molasses containing carrier material up to a three-month period.

An evaluation of the virtual simulated surgery assessment for the induction and return to practice scheme.

This paper reports on the development of the virtual Simulated Surgery assessment for the Induction and Return to practice (I&R) scheme and how it was used in the assessment of clinical and consultation skills. The evaluation examines the reliability and consistency of the virtual Simulated Surgery with the face-to-face assessment and reports feedback from the participants (candidates, administrators, marshals, examiners and role-players), highlighting what is lost and/or gained by the difference in format. Finally, the paper discusses the benefits and problems of remote assessment generally and looks at how this mode of assessment may be used in the future.

Exposure to cigarette smoke precipitates simple hepatosteatosis to NASH in high-fat diet fed mice by inducing oxidative stress.

Consumption of diet rich in fat and cigarette smoking (CS) are independent risk factors of non-alcoholic steatohepatitis (NASH), and they often occur together in some populations. The present study investigated the mechanisms of high-fat diet (HFD) and CS, individually and in combination, on the pathogenesis of NASH in mice. C57BL/6 male mice were subjected to either a low-fat chow (CH) or HFD with or without mainstream CS-exposure (4 cigarettes/day, 5 days/ week for 14 weeks). HFD alone caused hepatosteatosis (2.5-fold increase in TG content) and a significant increase in 3-nitrotyrisine (by ∼40-fold) but without an indication of liver injury, inflammation or fibrosis. CS alone in CH-fed mice increased in Tnfα expression and macrophage infiltration by 2-fold and relatively less increase in 3-nitrotyrosine (18-fold). Combination of HFD and CS precipitated hepatosteatosis to NASH reflected by exacerbated makers of liver inflammation and fibrosis which were associated with much severe liver oxidative stress (90-fold increase in 3-nitrotyrisine along with 6-fold increase in carbonylated proteins and 56% increase in lipid oxidations). Further studies were performed to administer the antioxidant tempol to CS exposed HFD mice and the results showed that the inhibition of liver oxidative stress prevented inflammatory and fibrotic changes in liver despite persisting hepatosteatosis. Our findings suggest that oxidative stress is a key mechanism underlying CS-promoted progression of simple hepatosteatosis to NASH. Targeting hepatic oxidative stress may be a viable strategy in halting the progression of metabolic associated fatty liver disease.

Epidemiology of molecular probes in Xpert MTB/RIF assay in Khyber Pakhtunkhwa, Pakistan.

Regardless of a plethora of advanced diagnostics, TB and drug resistance remains a principal killer. We proposed gold nanoparticles (AuNPs) attached with probes to enhance the efficiency of GeneXpert MTB/RIF assay instead of conventional dye probes for molecular detection. A total of 15,000 samples were collected from TB suspects and subjected to Xpert MTB/RIF assay, where 6800 (45.3%) were detected as MTB positive, 280 (4.3%) were detected to harbor mutations in the RRDR, while invalid /errors were found in 690 (4.6%) cases. The mutations were detected by probe E, 199 (71.1%), while probes B and D, 30 and 26 (10% and 9%), respectively. In the Xpert MTB/RIF Assay were found mutations picked by probes E and B codons 529-533 (71%) and 512-518 (10%), respectively. The fast-rising works of TB nano-diagnostics, of Xpert probes, may improve by the applications of gold nanoparticle probes.

SARS-CoV-2 nucleocapsid and Nsp3 binding: an in silico study.

Severe acute respiratory syndrome virus 2 (SARS-CoV-2) belongs to the single-stranded positive-sense RNA family. The virus contains a large genome that encodes four structural proteins, small envelope (E), matrix (M), nucleocapsid phosphoprotein (N), spike (S), and 16 nonstructural proteins (nsp1-16) that together, ensure replication of the virus in the host cell. Among these proteins, the interactions of N and Nsp3 are essential that links the viral genome for processing. The N proteins reside at CoV RNA synthesis sites known as the replication-transcription complexes (RTCs). The N-terminal of N has RNA-binding domain (N-NTD), capturing the RNA genome while the C-terminal domain (N-CTD) anchors the viral Nsp3, a component of RTCs. Although the structural information has been recently released, the residues involved in contacts between N-CTD with Nsp3 are still unknown. To find the residues involved in interactions between two proteins, three-dimensional structures of both proteins were retrieved and docked using HADDOCK. Residues at N-CTD were detected in interaction with L499, R500, K501, V502, P503, T504, D505, N506, Y507, I508, T509, K529, K530K532, S533 of Nsp3 and N-NTD to synthesize SARS-CoV-2 RNA. The interaction between Nsp3 and CTD of N protein may be a potential drug target. The current study provides information for better understanding the interaction between N protein and Nsp3 that could be a possible target for future inhibitors.

Structures of SARS-CoV-2 RNA-Binding Proteins and Therapeutic Targets.

BACKGROUND: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) epidemic has resulted in thousands of infections and deaths worldwide. Several therapies are currently undergoing clinical trials for the treatment of SARS-CoV-2 infection. However, the development of new drugs and the repositioning of existing drugs can only be achieved after the identification of potential therapeutic targets within structures, as this strategy provides the most precise solution for developing treatments for sudden epidemic infectious diseases. SUMMARY: In the current investigation, crystal and cryo-electron microscopy structures encoded by the SARS-CoV-2 genome were systematically examined for the identification of potential drug targets. These structures include nonstructural proteins (Nsp-9; Nsp-12; and Nsp-15), nucleocapsid (N) proteins, and the main protease (Mpro). Key Message: The structural information reveals the presence of many potential alternative therapeutic targets, primarily involved in interaction between N protein and Nsp3, forming replication-transcription complexes (RTCs) which might be a potential drug target for effective control of current SARS-CoV-2 pandemic. RTCs consist of 16 nonstructural proteins (Nsp1-16) that play the most essential role in the synthesis of viral RNA. Targeting the physical linkage between the envelope and single-stranded positive RNA, a process facilitated by matrix proteins may provide a good alternative strategy. Our current study provides useful information for the development of new lead compounds against SARS-CoV-2 infections.

Physician associate/assistant contributions to cancer diagnosis in primary care: a rapid systematic review.

BACKGROUND: Symptom recognition and timely referral in primary care are crucial for the early diagnosis of cancer. Physician assistants or associates (PAs) have been introduced in 18 healthcare systems across the world, with numbers increasing in some cases to address primary care physician shortages. Little is known about their impact on suspected cancer recognition and referral. This review sought to summarise findings from observational studies conducted in high income countries on PAs' competence and performance on processes concerned with the quality of recognition and referral of suspected cancer in primary care. METHOD: A rapid systematic review of international peer-reviewed literature was performed. Searches were undertaken on OVID, EMBASE, Web of Science, and CINAHL databases (2009-2019). Studies were eligible if they reported on PA skills, processes and outcomes relevant to suspected cancer recognition and referral. Title and abstract screening was followed by full paper review and data extraction. Synthesis of qualitative and quantitative findings was undertaken on three themes: deployment, competence, and performance. Preliminary findings were discussed with an expert advisory group to inform interpretation. RESULTS: From 883 references, 15 eligible papers were identified, of which 13 were from the USA. Seven studies reported on general clinical processes in primary care that would support cancer diagnosis, most commonly ordering of diagnostic tests (n = 6) and referrals to specialists (n = 4). Fewer papers reported on consultation processes, such as examinations or history taking (n = 3) Six papers considered PAs' competence and performance on cancer screening. PAs performed similarly to primary care physicians on rates of diagnostic tests ordered, referrals and patient outcomes (satisfaction, malpractice, emergency visits). No studies reported on the timeliness of cancer diagnosis. CONCLUSION: This review of peer-reviewed literature combined with advisory group interpretation suggests the introduction of PAs into primary care may maintain the quality of referrals and diagnostic tests needed to support cancer diagnosis. It also highlights the lack of research on several aspects of PAs' roles, including outcomes of the diagnostic process.

Genetic architecture of Al3+ toxicity tolerance in rice F2:3 populations determined through QTL mapping.

Aluminum (Al3+) toxicity is one of the factors limiting crop production in acidic soils. Identifying quantitative trait loci (QTLs)/genes for tolerance to Al3+ toxicity at seed germination can aid the development of new tolerant cultivars. The segregating population derived from Pak Basmati (Indica) × Pokkali (Indica) was used for mapping QTLs linked with tolerance to Al3+ toxicity ranging from 0 to 20 mM at pH 4 ± 0.2 at germination. The favorable alleles for all new QTLs were analyzed based on germination traits, i.e., final germination percentage (FG%), germination energy (GE), germination speed (GS), germination index (GI), mean germination time (MGT), germination value (GV), germination velocity (GVe), peak value of germination (GPV), and germination capacity (GC), and growth traits, such as root length (RL), shoot length (SL), total dry biomass (TDB) and germination vigor index (GVI). The phenotypic evolution showed transgressive variations. For genome-wide mapping, 90 polymorphic SSRs with 4 gene-specific markers and Win QTL Cart were used for QTL analysis. In all, 35 QTLs for germination and 11 QTLs for seedling growth were detected in distinct chromosomal regions by composite interval mapping (CIM), and multiple interval mapping (MIM) confirmed the pleiotropy at region RM128 on chromosome 1. Based on our genetic mapping studies, the genes/QTLs underlying tolerance to Al3+ toxicity could differ for both the germination and seedling stages in segregated populations. The QTLs identified in this study could be a source of new alleles for improving tolerance to Al3+ toxicity in rice.

On the influence of demographic structure and industrial growth on environmental quality.

The working-age population is an essential driver of economic growth that facilitates industrial growth, trade, and urbanization, but its impression on environmental quality is under-researched. This study proposes a novel framework to estimate the impact of demographic structure, industrial growth, and urbanization on two indicators of the environment (CO2 & Ecological footprints) in seven South Asian countries (SAARC) over 1985-2016 employing "Stochastic Impact by Regression on Population, Affluence, and Technology (STIRPAT)" framework. The results showed the variables have "cross-sectional dependence" and panel heterogeneity. Similarly, the Pedroni, Kao & Westerlund tests indicated the cointegration relationship between the models' chosen variables. The long-run empirical estimates imply that the linear term of industrial growth is negative. The quadratic term is positive, thus supporting the U-shaped Kuznets phenomenon in the SAARC countries. Similarly, the working-age population (demographic structure), urbanization, and trade are detrimental environmental quality indicators. The causal linkages developed between the variables duly verified the causality between demographic structure, urbanization, and industrial growth with environmental degradation based on ecological footprints and CO2 emissions. These results for SAARC countries offer important policies for theorists, academicians, and practitioners.

Covert nail injury to the back: A case report.

Occupational trauma in carpentry is common in our society due to lack of awareness on occupational safety and poor availability and adherence towards protective equipment. Given below is an unusual case of a young carpenter who presented in the orthopaedic outpatient department with complaint of difficulty in walking for the last four days. On examination, restricted movement of the hip joint on extension was observed. On further work up in the form of radiological investigations, a long iron nail was discovered as incidental finding in the back in close proximity to the ascending colon and duodenum in the retroperitoneum. Elective laparotomy was performed to remove the nail, after which the patient improved clinically and his presenting complaints were completely resolved on further follow up. This demonstrates the unusual way in which such a case can present in the outpatient department instead of the emergency department and with symptoms that may prompt one to think of anything but foreign body trauma, emphasising the need for proper history and meticulous relevant clinical examination, as covert foreign body injury can occur to the back, especially in patients involved in such occupations.

Burden of Drug resistant Tuberculosis in newly diagnosed Tuberculosis patients of Khyber Pakhtunkhwa, Pakistan.

OBJECTIVE: To explore the burden of drug-resistant tuberculosis in Khyber Pakhtunkhwa, Pakistan. METHODS: The cross-sectional study was conducted from March 1, 2016, to February 28, 2017, at the Khyber Pakhtunkhwa Tuberculosis Reference Laboratory, Hayatabad Medical Complex, Peshawar, Pakistan, and comprised referred suspected tuberculosis patient samples. Drug Susceptibility testing on all Mycobacterium tuberculosis complex strains was performed and data was subjected to statistical analysis. RESULTS: Of the 8220 samples, 4230 (51.5%) were related to females and 3990 (48.5%) to males. Also, 1978 (24%) were related to patients aged 15-24 years. Of the total, 1351 (16.5%) samples were positive on culture. Drug susceptibility testing showed 525 (39%) samples to be resistant to at least one of the first- and second-line drugs. Among the culture-positive cases, 5 (0.4%) were extensively drug-resistant, 62 (4.6%) multi-drug resistant, 243 (18%) polyresistant, 215 (16%) monoresistant and 826 (61%) were pan-sensitive. CONCLUSIONS: Drug-resistant tuberculosis in newly-diagnosed tuberculosis patients was alarmingly high in Khyber Pakhtunkhwa region.

The nexus of tourism, renewable energy, income, and environmental quality: an empirical analysis of Pakistan.

In the current study, we investigate the dynamic association of tourism, renewable energy, income, foreign direct investment (FDI), and carbon dioxide (CO2e) for Pakistan over 1990-2017. We established four plausible hypotheses and verified by employing the autoregressive distributed lags model and Granger causality based on vector error correction model (VECM). Considering the cointegration relationship between the variables, the outcomes of autoregressive distributed lags suggested that tourism increases economic growth, and economic growth induces tourism in the long-run, thus confirming tourism-led development, and growth-led tourism hypothesis; similarly, the tourism generates CO2e emissions, which supported the tourism-led emission hypothesis. The role of renewable energy consumption found to be a significant moderator, thus helping to enrich tourism, accelerating economic growth, and combating CO2e in the country. VECM causal results indicated the significant bidirectional causal linkages between tourism and economic growth-another causality found between tourism and CO2e. There is one-way causality from FDI and renewable energy towards income simultaneously. Overall, the designers of policies will find this study useful for policymaking at government levels for smooth economic growth, investment, and sustainable tourism sector.

Cigarette smoking blocks the benefit from reduced weight gain for insulin action by shifting lipids deposition to muscle.

Cigarette smoking (CS) is known to reduce body weight and this often masks its real effect on insulin action. The present study tested the hypothesis that CS can divert lipid deposition to muscles to offset the supposed benefit of reduced body weight gain on insulin signalling in this major site for glucose tolerance (or insulin action). The study was conducted in mice exposed to chronic CS followed by either a chow (CH) diet or a high-fat (HF) diet. CS increased triglyceride (TG) levels in both plasma and muscle despite a reduced body weight gain and adiposity. CS led to glucose intolerance in CH-fed mice and they retained the glucose intolerance that was induced by the HF diet. In adipose tissue, CS increased macrophage infiltration and the mRNA expression of TNFα but suppressed the protein expression of adipose triglyceride lipase and PPARγ. While CS increased hormone-sensitive lipase and suppressed the mRNA expression of leptin, these effects were blunted in HF-fed mice. These results imply that CS impairs insulin signalling in skeletal muscle via accumulated intramuscular lipids from lipolysis and lipodystrophy of adipose tissues. This may explain why smokers may not benefit from insulin sensitising effects of reduced body weight gain.