Orthopedic postoperative infection profile and antibiotic sensitivity of 2038 patients across 24 countries - Call for region and institution specific surgical antimicrobial prophylaxis.

Purpose: Improper utilization of surgical antimicrobial prophylaxis frequently leads to increased risks of morbidity and mortality.This study aims to understand the common causative organism of postoperative orthopedic infection and document the surgical antimicrobial prophylaxis protocol across various institutions in to order to strengthen surgical antimicrobial prophylaxis practice and provide higher-quality surgical care. Methods: This multicentric multinational retrospective study, includes 24 countries from five different regions (Asia Pacific, South Eastern Africa, Western Africa, Latin America, and Middle East). Patients who developed orthopedic surgical site infection between January 2021 and December 2022 were included. Demographic details, bacterial profile of surgical site infection, and antibiotic sensitivity pattern were documented. Results: 2038 patients from 24 countries were included. Among them 69.7 % were male patients and 64.1 % were between 20 and 60 years. 70.3 % patients underwent trauma surgery and instrumentation was used in 93.5 %. Ceftriaxone was the most common preferred in 53.4 %. Early SSI was seen in 55.2 % and deep SSI in 59.7 %. Western Africa (76 %) and Asia-Pacific (52.8 %) reported a higher number of gram-negative infections whereas gram-positive organisms were predominant in other regions. Most common gram positive organism was Staphylococcus aureus (35 %) and gram-negative was Klebsiella (17.2 %). Majority of the organisms showed variable sensitivity to broad-spectrum antibiotics. Conclusion: Our study strongly proves that every institution has to analyse their surgical site infection microbiological profile and antibiotic sensitivity of the organisms and plan their surgical antimicrobial prophylaxis accordingly. This will help to decrease the rate of surgical site infection, prevent the emergence of multidrug resistance and reduce the economic burden of treatment.

Unravelling the Road to Recovery: Mechanisms of Wnt Signalling in Spinal Cord Injury.

Spinal cord injury (SCI) is a complex neurodegenerative pathology that consistently harbours a poor prognostic outcome. At present, there are few therapeutic strategies that can halt neuronal cell death and facilitate functional motor recovery. However, recent studies have highlighted the Wnt pathway as a key promoter of axon regeneration following central nervous system (CNS) injuries. Emerging evidence also suggests that the temporal dysregulation of Wnt may drive cell death post-SCI. A major challenge in SCI treatment resides in developing therapeutics that can effectively target inflammation and facilitate glial scar repair. Before Wnt signalling is exploited for SCI therapy, further research is needed to clarify the implications of Wnt on neuroinflammation during chronic stages of injury. In this review, an attempt is made to dissect the impact of canonical and non-canonical Wnt pathways in relation to individual aspects of glial and fibrotic scar formation. Furthermore, it is also highlighted how modulating Wnt activity at chronic time points may aid in limiting lesion expansion and promoting axonal repair.

Synthesis, characterization and metal ions sensing applications of meta-benziporphodimethene-embedded polyacrylamide/carboxymethyl guargum polymeric hydrogels in water.

We have developed a robust procedure for the visual on-site detection of zinc, cadmium and mercury metal ions in an aqueous medium using a polymeric hydrogel matrix-based colorimetric sensor. Zn2+, Cd2+and Hg2+, owing to their biological significant value and environmental harm, have attracted more attention. The selective detection of Zn2+, Cd2+and Hg2+ metal ions has always been challenging due to their closed-shell d10 electronic configuration which makes them spectroscopically silent. A polyacrylamide/carboxymethyl guargum polymeric hydrogel-based metal ion sensor was synthesized by in situ embedding 11, 16-bis (phenyl)-6, 6, 21, 21-tetramethyl-m-benzi-6,21-porphodimethene (meta-BPDM) in a host hydrogel. The meta-BPDM-embedded hydrogel shows high stability, sensitivity and selectivity when it is dipped into the aqueous solutions of Zn2+, Cd2+and Hg2+ metal ions. During detection, the binding of these metal ions in hydrogel causes hydrogel to change from red to bluish-green which was visually detected and confirmed by UV-visible spectroscopy. The meta-BPDM-embedded polymeric hydrogel was characterized by using solid-state UV-visible spectroscopy, scanning electron microscopy, X-ray diffraction, thermogravimetric analysis, Fourier-transform infrared spectroscopy, energy-dispersive X-ray analysis and its sensing properties were studied. The meta-BPDM-embedded polymeric hydrogel was found to be an excellent colorimetric sensor for Zn2+, Cd2+ and Hg2+ in aqueous medium without leaching of meta-BPDM from the hydrogel. The selectivity to sense these ions is mainly dependent on the binding constant of these metal ions with the meta-BPDM embedded in the hydrogel. The sensitivity of the hydrogel was 0.5, 1, and 2 mg/L with Hg2+, Zn2+ and Cd2+, respectively.

Modified polymeric hydrogels for the detection of Zn2+ in E. coli bacterial cells and Zn2+, Cd2+ and Hg2+ in industrial effluents.

The article focusses on exploring the real-time application of meta-benziporphodimethene (m-BPDM) embedded polyacrylamide/carboxymethylguargum (PAM/CMG) hydrogel. The hydrogel-based sensor is highly selective for Zn2+, Cd2+ and Hg2+ with no significant response to other competitive cations including Na+, K+, Ca2+, Cr3+, Pb2+, Mg2+, Mn2+, Co2+, Cu2+ in aqueous medium. Initially, the stability of the hydrogel has been examined at different pH conditions. The sensitivity of the hydrogel was found to be 0.5, 1, and 2 ppm in 1, 2 and 3 h for Hg2+, Zn2+, and Cd2+, respectively, at pH 6. The sensor exhibits colour change from red to bluish-green with Zn2+, Cd2+ and Hg2+ in water over other ions. The modified hydrogel matrix displayed a unique naked eye turn-on colorimetric sensor selectivity for Zn2+, Cd2+ and Hg2+ ions in the aqueous solutions of Escherichia coli (E. coli) bacterial cells and industrial effluents. During the detection process, the zinc metal ions released because of cell lysis bind with hydrogel, in the former. The binding of Zn2+ causes the change in the colour of hydrogel from red to bluish-green, which was visually detected. The m-BPDM does not leach out and is stable in the hydrogel matrix. The sensing of Zn2+, Cd2+ and Hg2+ was achieved by directly adding hydrogel into industrial effluent without any pretreatment of effluent. The quantitative determination of Zn2+, Cd2+ and Hg2+ in industrial effluent was performed by the atomic absorption spectroscopy technique just to confirm the results obtained with the hydrogel.

Minimally invasive transforaminal lumbar interbody fusion - A narrative review on the present status.

Minimally invasive lumbar transforaminal interbody fusion (MIS TLIF) has become the most commonly performed lumbar fusion procedure. There are multiple variables such as bone graft properties, use of rhBMP (recombinant human bone morphogenic protein), interbody cage properties, image guidance techniques, etc., that may impact the outcomes and fusion rates. Radiation exposure to the patient as well as to the operating team is an important concern. The minimally invasive anterior approaches for lumbar fusion with ability to insert larger cages and achieve better sagittal correction have added another option in management of lumbar degenerative deformities. A literature review of recent studies and systematic reviews on different aspects impacting the outcomes of MIS TLIF has been done to define the present status of the procedure in this narrative review. Iliac crest bone graft can help achieve very good fusion rate without significantly increasing the morbidity. RhBMP is most potent enhancer of fusion and the adverse effects can be avoided by surgical technique and using lower dose. The use of navigation techniques has reduced the radiation exposure to patient and the surgeons but the benefit seems to be significant only in long segment fusions.

Is there an interdependence between paraspinal muscle mass and lumbar disc degeneration? A MRI based study at 2520 levels in 504 patients.

INTRODUCTION: Low back pain is one of the most common cause for outpatient visits. Though few studies have shown the vital role of paraspinal muscles in lumbar spine pathology, literature is scarce regarding the influence of the paraspinal muscles in disc degeneration. We aimed to analyse the correlation between paraspinal muscles and disc degeneration. METHODS: This is a Level III Prospective Cohort Study done in MRI of lumbosacral spine in 504 patients at 2520 levels from L1-2 to L5-S1. The parameters assessed were age, Pfirrmann grade for disc degeneration and paraspinal muscle (Multifidus and Erector Spinae) mass assessed by the gross cross sectional area of the muscle.The values and their correlation was analyzed using SPSS software. RESULTS: The study included a total of 504 patients (231 males and 273 females) with a mean age of 52.00 ± 15.00 (22-80) years. The mean GCSA in cm2 of the paraspinal muscles at L1-L2, L2-L3,L3-L4,L4-L5,L5-S1 were 16.177 ± 2.72, 17.275 ± 2.16, 16.900 ± 3.07, 16.800 ± 2.63, 13.426 ± 2.42 respectively. We found that the age of the patient is directly proportional to the disc degeneration and inversely proportional to GCSA of paraspinal muscle. There was a significant negative correlation between disc degeneration and paraspinal muscle mass. CONCLUSION: We found that the paraspinal muscle mass reduces and Pfirrman's Grade increases as age advances. Also patients with disc degeneration tend to have wasting of paraspinal muscles and vice versa. Hence, strengthening the paraspinal muscles should be emphasised to prevent back pain and to stall the degeneration cascade.

Epithelioid Sarcoma of Lumbar Spine: A Rare Mesenchymal Tumor Masquerading as Infection.

Epithelioid sarcoma of the spine has been rarely reported in the literature. Its diagnosis is challenging due to nonspecific findings. We report a case of 42-year-old gentleman with back pain. Magnetic resonance imaging (MRI) revealed lesion in the L4 vertebral body extending into the spinal canal with pre and paravertebral involvement. He underwent posterior spinal decompression and instrumentation with biopsy. Histopathological examination was nonspecific. Considering clinical and radiological features, antitubercular treatment was initiated. The patient developed acute onset weakness of both lower extremities 1 month post-surgery. Repeat MRI and positron emission tomography (PET) computed tomography revealed an increase in the extent of lesion which required revision decompression. Histopathological examination showed cells with epithelioid appearance, positive for Vimentin, and epitheloid membrane antigen in immunohistochemistry. Radiotherapy was planned but the patient expired due to multiorgan dysfunction. Epithelioid sarcomas are rare soft-tissue neoplasms with poor prognosis. They can mimic infection and a high degree of suspicion is required in these cases to diagnose and treat them early.

Posttraumatic thoracic epidural capillary hemangioma - A rare case report.

BACKGROUND: Capillary hemangiomas are benign vascular lesions commonly seen in subcutaneous tissues. The most common site of origin is from the vertebral body, and only a few cases of isolated lesions in thoracic epidural space, especially after trauma, have been reported in the literature. CASE DESCRIPTION: We report a case of 63-year-old male with progressive bilateral lower limb weakness and exaggerated lower limb deep tendon reflexes without bowel and bladder involvement. His history revealed T7 fracture with paraparesis which was treated surgically, and implants were removed a year later. MRI showed an epidural lesion from T6-T8 extending into the right T7-8 foramen which showed hypointensity on T1, hyperintensity on T2, and homogenous enhancement in contrast images with severe cord compression. Laminectomy was done and the lesion was removed en bloc. Histopathological examination revealed it to be capillary hemangioma. The neurology came back to normal after 3 months. CONCLUSION: Although capillary hemangiomas are rare lesions, it has to be considered in the differential diagnosis of epidural space-occupying lesions which require early surgical removal to prevent a progressive and permanent neurological deficit.

Does Type II Diabetes Induce Early Senescence and Degeneration in Human Intervertebral Discs? A Tissue Biomarker Evaluation.

BACKGROUND: Diabetes mellitus is one of the leading causes of morbidity resulting in multi-organ dysfunction. Animal studies have shown that hyperglycemia results in stress-induced senescence through the p16-pRb pathway, thereby accelerating early disc degeneration. There is a paucity of literature on the effect of hyperglycemia in human intervertebral disc cells. We aimed to analyze the effect of diabetes mellitus in human intervertebral disc cells. METHODS: This is a prospective study done in patients with degenerative disc disease. Patients were categorized into a control group (no diabetes: 26 patients) and a study group (type 2 diabetes for > 3 years: 24 patients). All patients underwent either discectomy or transforaminal lumbar interbody fusion and the removed disc was transported to pathology department. Tissue was prepared and histopathological grading was done followed by immunohistochemistry studies using antibodies for MMP-1, p21, p16, and pRb. RESULTS: Samples from diabetic patients had severe (grade 2) degenerative changes compared with the control group (grade 1). Changes were more intense in the nucleus pulposus with increased cellularity and clustering of chondrocytes, and disorganization and loss of nuclear matrix. Immunohistochemical staining for MMP1, p16, and pRb was more intense (Q score = 4) whereas the staining for p21 was less intense (Q score = 1) in the diabetic group compared with the control group. CONCLUSION: Our study demonstrates that type 2 diabetes mellitus accelerates stress-induced senescence in human intervertebral discs resulting in early disc degeneration. Also, the severity of disc degeneration is severe compared with the normal subjects. CLINICAL RELEVANCE: Hyperglycemia can affect the intervertebral discs similar to other organs and hence adequate control of blood glucose in diabetics can prevent the disc degeneration, which is the initiator of degeneration cascade in spine.

Analysis of factors influencing ligamentum flavum thickness in lumbar spine - A radiological study of 1070 disc levels in 214 patients.

OBJECTIVE: The pathomechanism and factors influencing hypertrophy of the Ligamentum flavum in the lumbar spine still requires a confident specificity. We aimed to analyse the association between various factors and Ligamentum Flavum Thickness (LFT) and also to investigate the major contributor for Ligamentum Flavum Hypertrophy (LFH) at various levels in the lumbar spine. PATIENTS AND METHODS: The following were evaluated at L1-L2,L2-L3,L3-L4,L4-L5 and L5-S1 levels in MRI of 1070 lumbar disc levels of 214 subjects: Pfirrmann's grade of the disc, anterior and posterior disc height, disc volume, facet tropism and LFT. LFT > 0.4 cm was considered as hypertrophy.Correlation between LFT and other parameters was done and values with p < 0.05 was considered statistically significant. RESULTS: 112 male and 102 female were included. There was an increase in the anterior disc height (0.98 cm to 1.50 cm), posterior disc height (0.84 cm to 0.96 cm), disc volume (7.17cm3 to 14.6cm3), facetal angle and LFT on both sides from L1-2 to L5-S1 levels. Highest frequency of LFT was seen at L4-5.Pfirrmann's grade of the disc and anterior disc height had a statistically significant positive correlation with LFT at L1-L2,L2-L3,L3-L4,L4-L5 levels whereas facet tropism was strongly associated with LFT at L5-S1 level. CONCLUSION: Higher Pfirrmann's grade and decreased anterior disc height can lead to ligamentum flavum hypertrophy at L1-L2, L2-L3,L3-L4,L4-L5 levels.Whereas at L5-S1 level, it is the presence of facet tropism which can cause LFH. Hence, patients with the presence of above mentioned factors at those respective levels have higher preponderance to develop Lumbar canal stenosis.

Extraction optimization of pectin from cocoa pod husks (Theobroma cacao L.) with ascorbic acid using response surface methodology.

Cocoa husks were used as the source for the pectin extraction by sugar acid treatment. A full factorial design was applied to screen the independent variables influencing the yield and uronic acid content. Followed by response surface methodology (RSM) was conducted using central composite design to optimize the extraction conditions. The optimized extraction condition was denoted as pH 2.5/95 °C/45 min. The yield and the uronic acid content of the extracted pectin was determined as 4.2 ± 0.12% and 74.5 ± 0.3% respectively. The extracted pectin was proved to be low methoxy pectin (LM pectin) with an 8.1% degree of esterification (DE). The pectin solutions showed shear thinning behaviour which was explicated by Williamson model. This work promotes environmentally friendly technology for pectin isolation.

Compartment syndrome of lumbar paraspinal musculature after percutaneous pedicle screw fixation.

BACKGROUND: Compartment syndromes have been reported in nearly every anatomical area of the extremities. Similarly, in the lumbar spine, there is a risk of a compartment syndrome following either direct or indirect injury to the paraspinal muscles. In this study, we present a case of lumbar paraspinal compartment syndrome after percutaneous pedicle screw fixation for a spine fracture. CASE DESCRIPTION: A 27-year-old obese female sustained a fall and an L1 fracture. Her neurological examination was normal. She underwent a minimally invasive percutaneous posterior pedicle screw fixation from T12 to L2 to stabilize the L1 fracture. Postoperatively, the patient developed hypoesthesia in the back, and sterile serous wound discharge. Because of the persistent discharge, an open debridement was performed that revealed multiple cavities within the necrotic avascular paraspinal musculature. Once these were completely excised, the wounds healed uneventfully. CONCLUSION: Patients undergoing minimally invasive posterior thoracolumbar (TL) pedicle screw fixation can develop a compartment syndrome involving the TL paraspinal musculature. This case highlights the need for early consideration of a compartment syndrome when patients develop persistent sterile discharge after spine surgery. In this case, urgent decompression prevented any long-term sequelae.

microRNA-184 Induces a Commitment Switch to Epidermal Differentiation.

miR-184 is a highly evolutionary conserved microRNA (miRNA) from fly to human. The importance of miR-184 was underscored by the discovery that point mutations in miR-184 gene led to corneal/lens blinding disease. However, miR-184-related function in vivo remained unclear. Here, we report that the miR-184 knockout mouse model displayed increased p63 expression in line with epidermal hyperplasia, while forced expression of miR-184 by stem/progenitor cells enhanced the Notch pathway and induced epidermal hypoplasia. In line, miR-184 reduced clonogenicity and accelerated differentiation of human epidermal cells. We showed that by directly repressing cytokeratin 15 (K15) and FIH1, miR-184 induces Notch activation and epidermal differentiation. The disease-causing miR-184C57U mutant failed to repress K15 and FIH1 and to induce Notch activation, suggesting a loss-of-function mechanism. Altogether, we propose that, by targeting K15 and FIH1, miR-184 regulates the transition from proliferation to early differentiation, while mis-expression or mutation in miR-184 results in impaired homeostasis.

Differential Impact of Glucose Administered Intravenously and Orally on Circulating miR-375 Levels in Human Subjects.

Background: To date, numerous nucleic acid species have been detected in the systemic circulation including microRNAs (miRNAs); however, their functional role in this compartment remains unclear. Objective: The aim of this study was to determine whether systemic levels of miRNAs abundant in blood, including the neuroendocrine tissue-enriched miR-375, are altered in response to a glucose challenge. Design: Twelve healthy males were recruited for an acute crossover study that consisted of two tests each following an 8-hour fasting period. An oral glucose tolerance test (OGTT) was performed, and blood samples were collected over a 3-hour period. Following a period of at least 1 week, the same participants were administered an isoglycemic intravenous glucose infusion (IIGI) with the same blood-collection protocol. Results: The glucose response curve following the IIGI mimicked that obtained after the OGTT, but as expected, systemic insulin levels were lower during the IIGI compared with the OGTT (P < 0.05). miR-375 levels in circulation were increased only in response to an OGTT and not during an IIGI. In addition, the response to the OGTT also coincided with the transient increase of circulating glucagon-like peptide (GLP)-1, GLP-2, and glucose-dependent insulinotropic polypeptide. Conclusions: The present findings show levels of miR-375 increase following administration of an OGTT and, in light of its enrichment in cells of the gut, suggest that the gastrointestinal tract may play an important role in the abundance and function of this miRNA in the blood.

Sacral Insufficiency Fractures Mimicking Lumbar Spine Pathology.

Sacral insufficiency fractures (SIFs) are a common cause of back pain in the elderly. SIFs mimic the symptoms of lumbar spine pathology and so are commonly missed or underdiagnosed. Here we present four cases of missed SIFs that were subsequently identified and treated. One patient was treated as mechanical lower back ache, another patient underwent root block and two patients underwent surgery for lumbar canal stenosis. None experienced relief of their symptoms after these procedures. Retrospective analysis of X-ray and magnetic resonance imaging data revealed SIFs that were confirmed by computed tomography scans. All four patients were treated for underlying osteoporosis. Two patients who underwent surgery were treated conservatively and other two were treated by sacroplasty involving injection of cement into the fracture. Sacroplasty produced immediate pain relief and early mobilization compared to the conservative group. SIFs should always be considered in the differential diagnosis of an elderly patient presenting with low back symptoms. Sacroplasty can be considered for immediate pain relief and rapid mobilization.

Radiographic Analysis of the Sacropelvic Parameters of the Spine and Their Correlation in Normal Asymptomatic Subjects.

Study Design Cross-sectional study. Objective Sacropelvic parameters in various spine and hip disorders have been published in various studies. We aimed to study the normal sacropelvic parameters and curvatures of the spine and their correlation in asymptomatic Indian adults in relation to variations in sex and age. Methods The study included 101 asymptomatic adults (50 men and 51 women with an average age of 47.16 and 48.59 years, respectively). For each subject, the thoracic kyphosis (TK), lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS) were measured from standing lateral radiographs. After stratification of the group by sex and age with a cutoff of 50 years, descriptive, correlation, and regression analysis were performed using SPSS software. Results The average PI, SS, PT, LL, and TK values were 55.48 (±5.31), 35.99 (±7.53), 17.97 (±7.16), 48.84 (±9.82), and 32.55 (±10.92), respectively. No statistically significant difference was observed in these values with regards to sex and age < 50 years and > 50 years but the pelvic incidence was found to be higher in women. A positive correlation between the PI and SS and a negative correlation between the SS and PT was observed. A positive correlation between the TK and LL was found in subjects > 50 years. Simple and multiple regression analyses were also performed for different groups. Conclusion The current study is the first of asymptomatic Indian adults and provides invaluable information to the clinicians about the normal range of sacropelvic and spinopelvic parameters, which is useful to plan spinal deformity corrections and to evaluate pathologic conditions associated with abnormal angular values.

miR-184 Regulates Pancreatic ß-Cell Function According to Glucose Metabolism.

In response to fasting or hyperglycemia, the pancreatic ß-cell alters its output of secreted insulin; however, the pathways governing this adaptive response are not entirely established. Although the precise role of microRNAs (miRNAs) is also unclear, a recurring theme emphasizes their function in cellular stress responses. We recently showed that miR-184, an abundant miRNA in the ß-cell, regulates compensatory proliferation and secretion during insulin resistance. Consistent with previous studies showing miR-184 suppresses insulin release, expression of this miRNA was increased in islets after fasting, demonstrating an active role in the ß-cell as glucose levels lower and the insulin demand ceases. Additionally, miR-184 was negatively regulated upon the administration of a sucrose-rich diet in Drosophila, demonstrating strong conservation of this pathway through evolution. Furthermore, miR-184 and its target Argonaute2 remained inversely correlated as concentrations of extracellular glucose increased, underlining a functional relationship between this miRNA and its targets. Lastly, restoration of Argonaute2 in the presence of miR-184 rescued suppression of miR-375-targeted genes, suggesting these genes act in a coordinated manner during changes in the metabolic context. Together, these results highlight the adaptive role of miR-184 according to glucose metabolism and suggest the regulatory role of this miRNA in energy homeostasis is highly conserved.

Laparoscopic Peptic Ulcer Perforation Closure: the Preferred Choice.

Peptic ulcer perforation is a common life-threatening emergency needing immediate intervention. Laparoscopic closure of perforation is now widely practiced over conventional open closure. This study aimed to compare laparoscopic peptic ulcer perforation closure with conventional open closure in terms of operative time, postoperative analgesia, complications, hospital stay, and return to routine activities. This unicentric, nonblinded, prospective, randomized study was carried out in 50 patients with peptic ulcer perforation who were randomly allocated to undergo either laparoscopic closure or open closure surgery with 25 patients in each group. The mean operative time (60 vs 90 min) was less in the laparoscopic group (p < 0.05). Postoperative analgesia requirements (1 vs 6 days) were also less in laparoscopic patients (p < 0.05). Complications (nil vs 6; p < 0.05) and hospital stay (3 vs 8 days) were less in laparoscopic patients (p < 0.05). Patients return to normal activities (5 vs 10 days; p < 0.05) earlier in laparoscopic perforation closure than in open closure. Our study has shown better outcomes and lesser morbidities with laparoscopic approach in terms of shorter operative time, shorter hospital stay, less analgesic requirements, and less wound infections. Patients also return to routine activities earlier with the laparoscopic approach. It is a safe alternative to open surgery and should be a preferred choice when there are no contraindications to laparoscopy.

Argonaute2 mediates compensatory expansion of the pancreatic ß cell.

Pancreatic ß cells adapt to compensate for increased metabolic demand during insulin resistance. Although the microRNA pathway has an essential role in ß cell proliferation, the extent of its contribution is unclear. Here, we report that miR-184 is silenced in the pancreatic islets of insulin-resistant mouse models and type 2 diabetic human subjects. Reduction of miR-184 promotes the expression of its target Argonaute2 (Ago2), a component of the microRNA-induced silencing complex. Moreover, restoration of miR-184 in leptin-deficient ob/ob mice decreased Ago2 and prevented compensatory ß cell expansion. Loss of Ago2 during insulin resistance blocked ß cell growth and relieved the regulation of miR-375-targeted genes, including the growth suppressor Cadm1. Lastly, administration of a ketogenic diet to ob/ob mice rescued insulin sensitivity and miR-184 expression and restored Ago2 and ß cell mass. This study identifies the targeting of Ago2 by miR-184 as an essential component of the compensatory response to regulate proliferation according to insulin sensitivity.