Evaluation of Fracture Resistance of Reattached Fractured Tooth Fragment Stored in Different Storage Media: An In Vitro Study.

AIM: To evaluate the fracture resistance of coronal fractured tooth fragments stored in five different storage media when reattached with nanohybrid flowable composite. MATERIALS AND METHODS: The crown portion of 50 extracted human permanent maxillary central incisors were divided into three equal parts (incisal third, middle third and cervical third) and then marked incisal third were cut with the diamond disk. These were divided into five equal groups according to the type of storage media used i.e. dry storage, fresh tender coconut water, HBSS, milk, and propolis for 2 hours. Coronal fractured part with their respective apical parts were then reattached with flowable composite (G-aenial Universal Flo, GC India), then after thermocycling process samples were subjected to universal testing machine for testing fracture resistance. The collected data were subjected to statistical analysis using one way ANOVA and Post-hoc Tukey test. RESULTS: The obtained results revealed that large amount of force is required to fracture the reattached teeth which were stored in milk and fresh tender coconut water as compared to those which were stored in dry environment, HBSS and propolis. CONCLUSION: In this study, maximum fracture resistance was seen in teeth stored in milk and fresh tender coconut water. Therefore, these two were considered as better storage media. CLINICAL SIGNIFICANCE: Due to increased interest towards the use of tooth colored restoration, recently, fractured teeth reattachment treatment procedure gaining attention by preserving life like translucency of treated tooth.

Evaluation of Sealing Ability of Three Root Canal Sealers: An In Vitro Study.

AIM: To evaluate the sealing ability of three different types of sealers using confocal laser microscopy. MATERIALS AND METHODS: Sixty extracted single-root premolars were selected and divided into three groups (20 teeth in each group) according to the type of sealer used, namely, mineral trioxide aggregate (MTA) Fillapex, AH Plus, and Bio C Sealer. Root canal preparation and obturation were done in all the samples. Roots was dissected transversely in apical plane. Percentage of gap from region to canal circumference was calculated using a confocal laser microscope. Samples were subjected to statistical analysis. RESULTS: High dye penetration was seen with AH Plus compared to MTA Fillapex and least with Bio C Sealer. The AH Plus is the best sealer with respect to seal ability of all the three. CONCLUSION: This study helps to appraise the sealing ability of the different types of sealers using confocal laser microscopy which is useful for the success of root canal treatment. CLINICAL SIGNIFICANCE: As sealer has to seal voids, foramina, and canals, it should have good penetration for the success of root canal treatment.

Robot-assisted retroperitoneal lymph node dissection: Feasibility and outcome in postchemotherapy residual mass in testicular cancer.

INTRODUCTION: We aimed to evaluate the surgical feasibility, complication, and oncological outcome of robot-assisted retroperitoneal lymph node dissection (RA-RPLND) in patients of testicular tumor with postchemotherapy residual retroperitoneal mass. METHODS: A total of 13 patients underwent RA-RPLND between January 2012 and September 2016 at our institute. A study was started on December 2015, so data were collected retrospectively and prospectively regarding patient demography, tumor characteristics, surgical, pathological outcome, and oncological outcome. RESULTS: RA-RPLND was successfully completed in all the 13 patients. Lateral approach was used in initial 12 patients with unilateral dissection in 11 patients and bilateral dissection after in 1 patient after repositioning in bilateral position. Supine robotic approach used in 1 patient. Median operative time was 200 min, median estimated blood loss was 120 ml, and median length of hospital stay was 4 days. The median yield of lymph node was 20. Three patients had positive lymph nodes, all had teratoma germ cell tumor. Ten patients had only necrosis in lymph nodes. After median follow-up 23 months (range 3-58 months), no systemic or retroperitoneal recurrence was found. Four patients developed chyle leak. One patient was managed conservatively with diet modification, one with intranodal lipiodol lymphangiography and two patients were managed surgically. CONCLUSION: RA-RPLND is safe and feasible for postchemotherapy residual mass with accepted compilation rate, but larger studies are required to establish its diagnostic and therapeutic utility along with safety of the procedure.

A rare case of leptospirosis with isolated lung involvement.

Leptospirosis is a zoonosis caused by a pathogenic spirochete "leptospira interrogans." Severe form of leprospira infection is usually associated with jaundice and renal involvement, leading to major hemorrhagic complications. Lung involvement can vary from subtle clinical features to deadly pulmonary hemorrhage and acute respiratory distress syndrome (ARDS). We recently managed a case of leptospirosis with isolated lung involvement as alveolar hemorrhage and ARDS. Our patient had acute febrile illness with respiratory symptoms associated with radiological picture of pulmonary hemorrhage. Patient was managed with noninvasive ventilation with high flow oxygen, antibiotic and pulse steroids therapy. In conclusion, leptospirosis can present with predominant pulmonary involvement, instead of the classical triad of Weil disease. High index of suspicion should be kept in acute febrile illness patients with respiratory symptoms and alveolar hemorrhage. Early diagnosis and management with oxygenation, antibiotics and immunosuppresents can prevent complications and mortality.

Aluminum phosphide poisoning: Possible role of supportive measures in the absence of specific antidote.

Aluminum phosphide (ALP) poisoning is one of the major causes of suicidal deaths. Toxicity by ALP is caused by the liberation of phosphine gas, which rapidly causes cell hypoxia due to inhibition of oxidative phosphorylation, leading to circulatory failure. Treatment of ALP toxicity is mainly supportive as there is no specific antidote. We recently managed 7 cases of ALP poisoning with severe hemodynamic effects. Patients were treated with supportive measures including gastric lavage with diluted potassium permanganate, coconut oil and sodium-bicarbonate first person account should be avoided in a scientific paper. Intravenous magnesium sulfate, proper hemodynamic monitoring and vasopressors. Four out of 7 survived thus suggesting a role of such supportive measures in the absence of specific antidote for ALP poisoning.

Potassium permanganate toxicity: A rare case with difficult airway management and hepatic damage.

Potassium permanganate (KMnO4) is rarely used for suicidal attempt. Its ingestion can lead to local as well as systemic toxicities due to coagulation necrosis and damage, caused by free radicals of permanganate. We recently managed a case of suicidal ingestion of KMnO4 in a lethal dose. She had significant narrowing of upper airway leading to difficult intubation as well as hepatic dysfunction and coagulopathy as systemic manifestation. We suggest to keep ourselves ready to handle difficult airway with the aid of fiber optic bronchoscope or surgical airway management in such patients. Upper gastrointestinal (GI) endoscopy should be done at the earliest to determine the extent of upper GI injury and further nutrition planning.

Neutrophil Gelatinase-Associated Lipocalin (NGAL) as a potential early biomarker for diabetic nephropathy: a meta-analysis.

BACKGROUND: Diabetic nephropathy (DN) is a prevalent and chronic, severe complication of diabetes, representing a serious global health concern. Early detection of DN is essential for initiating timely and effective therapeutic interventions and accurately assessing prognosis. Neutrophil Gelatinase-Associated Lipocalin (NGAL), a low molecular weight protein, has emerged as a potential biomarker for DN due to its association with renal injury and its ability to provide early indications of kidney damage. NGAL levels in both serum and urine are elevated in individuals with renal damage, making it a valuable biomarker for detecting early signs of kidney impairment in the context of diabetes. This study aims to investigate the utility of NGAL as an early biomarker for DN and explore its correlation with various clinical parameters associated with the disease. Understanding the relationship between NGAL levels and clinical parameters such as glycemic control, renal function, blood pressure, and duration of diabetes is crucial for comprehensively evaluating the potential of NGAL as a diagnostic and prognostic tool for DN. Furthermore, assessing the sensitivity and specificity of NGAL in detecting early-stage DN will provide valuable insights into its clinical applicability and reliability. METHODOLOGY: A planned meta-analysis was conducted following PRISMA and MOOSE guidelines. The PubMed database was searched from January 2016 to June 2023 for English-language studies on DN and NGAL. Fifteen eligible studies were included as per the criteria. Data on serum NGAL levels in DN patients and healthy controls were analyzed using Stata 16.0 software. RESULT: The study revealed a significantly higher mean serum NGAL level in DN patients (168.08 ng/ml, 95% CI: 105.50-230.67) compared to healthy controls (75.02 ng/ml, 95% CI: 43.02-107.03), demonstrating NGAL's potential as a biomarker (P=0.01). CONCLUSION: NGAL offers a powerful tool for DN diagnosis, staging, and monitoring, surpassing traditional markers in sensitivity. Challenges include defining universal threshold values and ensuring consistent test performance across diverse clinical settings. The study underscores NGAL's potential in transforming DN diagnosis and management.

AI-based pipeline for early screening of lung cancer: integrating radiology, clinical, and genomics data.

Background: The prognosis of lung carcinoma has changed since the discovery of molecular targets and their specific drugs. Somatic Epidermal Growth Factor Receptor (EGFR) mutations have been reported in lung carcinoma, and these mutant proteins act as substrates for targeted therapies. However, in a resource-constrained country like India, panel-based next-generation sequencing cannot be made available to the population at large. Additional challenges such as adequacy of tissue in case of lung core biopsies and locating suitable tumour tissues as a result of innate intratumoral heterogeneity indicate the necessity of an AI-based end-to-end pipeline capable of automatically detecting and learning more effective lung nodule features from CT images and predicting the probability of the EGFR-mutant. This will help the oncologists and patients in resource-limited settings to achieve near-optimal care and appropriate therapy. Methods: The EGFR gene sequencing and CT imaging data of 2277 patients with lung carcinoma were included from three cohorts in India and a White population cohort collected from TCIA. Another cohort LIDC-IDRI was used to train the AIPS-Nodule (AIPS-N) model for automatic detection and characterisation of lung nodules. We explored the value of combining the results of the AIPS-N with the clinical factors in the AIPS-Mutation (AIPS-M) model for predicting EGFR genotype, and it was evaluated by area under the curve (AUC). Findings: AIPS-N achieved an average AP50 of 70.19% in detecting the location of nodules within the lung region of interest during validation and predicted the score of five lung nodule properties. The AIPS-M machine learning (ML) and deep learning (DL) models achieved AUCs ranging from 0.587 to 0.910. Interpretation: The AIPS suggests that CT imaging combined with a fully automated lung-nodule analysis AI system can predict EGFR genotype and identify patients with an EGFR mutation in a cost-effective and non-invasive manner. Funding: This work was supported by a grant provided by Conquer Cancer Foundation of ASCO [2021IIG-5555960128] and Pfizer Products India Pvt. Ltd.

Comparison of BTP, NGAL, KIM-1, & ADMA biomarkers in CKD and non-CKD subjects.

INTRODUCTION: New biomarkers, such as neutrophil gelatinase-associated lipocalin (NGAL), a member of the lipocalin family, and kidney injury molecule-1 (KIM-1) have been utilised in recent years to identify the development of chronic kidney disease (CKD). However, attempts to use them as broad markers to check for renal injury in patients and to pinpoint the kidney injury site have been unsuccessful. Therefore the search for an ideal panel of biomarkers predicting progression of CKD is still ongoing. The present study is designed to evaluate the biomarkers for CKD from NGAL, KIM-1, Beta trace protein (BTP) and Asymmetric dimethylarginine (ADMA). MATERIALS AND METHODS: For this case-control study, 100 participants were selected on the basis of inclusion and exclusion criteria at the Index Medical College Hospital and Research Centre, Madhya Pradesh, there were 67 male subjects and 33 female CKD subjects and 100 non-CKD subjects (60 male and 40 female) matched for age and sex were taken from the hospital. RESULTS: Between the CKD and non-CKD participants, the levels of BTP, plasma NGAL, KIM-1, and ADMA were compared and found to be substantially higher than those in the controls. CONCLUSION: Abnormal renal function is linked to disturbed blood levels of BTP, NGAL, KIM-1, and ADMA. Strong correlations exist between increased blood levels of BTP, NGAL, KIM-1, and ADMA and reduced kidney function. They might thus be used to estimate the decline of renal function and the progression of CKD.

A novel EML4-NTRK3 fusion in lung adenocarcinoma with dramatic response to entrectinib.

ABSTRACT: In-frame fusions in NTRK genes, with intact kinase domain, have been reported to occur at higher frequencies in rare tumors like infantile fibrosarcoma, congenital mesoblastic nephroma, and secretory carcinoma, whereas they occur at very low frequencies in common malignancies like NSCLC and colon cancers (0.1%-1%). Despite the rare occurrence, these alterations have gained importance owing to approval of drugs like entrectinib and larotrectinib targeting the kinase domain of the gene. More than 50 fusion partners have been described, and only in-frame fusions result in constitutive ligand-independent kinase activity leading to oncogenesis. The commonly reported NTRK fusions in the lung include SQSTM1-NTRK1, ETV6-NTRK3, and SQSTM1-NTRK3. Detection of these rests on the use of conventional modalities like Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH); however, accurate characterization requires direct sequencing methods. We report an interesting case of an NTRK fusion-positive NSCLC, exhibiting good response to entrectinib.

Autoimmune Thyroid Disease in Psoriasis Patients: A Case-Control Study.

INTRODUCTION: Psoriasis is a common immunologically mediated inflammatory disease characterized by skin inflammation, epidermal hyperplasia, an increased risk of painful and destructive arthritis, cardiovascular morbidity, and psychosocial challenges. Some autoimmune diseases are mediated by stimulating or blocking auto-antibodies. Auto-antibodies may act as antagonists and bind to hormone receptors, blocking receptor function. It may result in impaired secretion of mediators and gradual dysfunction of the affected organ, e.g., Graves disease and myasthenia gravis. OBJECTIVE: This study was planned to evaluate the association between anti-thyroid peroxidase antibody (anti-TPO Ab) and anti-thyroglobulin antibody (anti-TG Ab) as biochemical markers in 30 clinically diagnosed psoriasis patients. MATERIALS AND METHODS: This hospital-based, epidemiological case-control study was conducted in the Department of Biochemistry in collaboration with the Department of Dermatology, Venereology, and Leprology at Bhagat Phool Singh Government Medical College for Women, Khanpur Kalan, Sonepat, Haryana, India. Thirty subjects diagnosed clinically with psoriasis and an equal number of age-matched controls with no known autoimmune disease from the outpatient department were also enrolled. The following hormonal tests, i.e., thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), and antibodies, anti-TPO Ab and anti-TG Ab, were performed. The study period was one year. The data thus obtained was analyzed using SPSS Statistics version 26.0 (IBM Corp. Released 2019. IBM SPSS Statistics for Windows, Version 26.0. Armonk, NY: IBM Corp). The significance level (p-value) was taken as <0.05. RESULTS: The mean age of psoriasis subjects was 37.83±12.89 years compared to 36.91±12.32 years in the control group and was found to be non-significant (p=0.432), reflecting a similar age distribution. A male preponderance was observed in the present study, where the psoriasis group consisted of 80% males and 20% females, while the control group had 60% males and 40% females. All six psoriasis patients diagnosed with autoimmune thyroid disease (AITD) were euthyroid at the time of enrollment, compared to only one control subject in a subclinical hypothyroid state. The mean values of anti-TPO Ab were 30.93±41.26 IU/mL in psoriasis patients and 11.39±28.42 IU/mL in the control group (p=0.001), while the mean values of anti-TG Ab were 11.21±27.69 IU/mL in psoriatic subjects and 2.49±9.05 IU/mL in the control group (p=0.004). No significant correlation between AITD and psoriasis was found when both parameters were analyzed statistically for correlation; even when one marker was considered, no significant correlation was found. The odds ratio was calculated to find an association between the disease and thyroid autoimmunity. The odds ratio was estimated to be 2.25 for psoriasis and the control group, with a confidence interval of 95% (0.77-6.59) and a p-value of 0.139, which was not statistically significant. CONCLUSION: Psoriasis, a dermatological disorder, has been seen as related to AITD. The role of early detection of anti-thyroid antibodies, i.e., anti-TPO Ab and anti-TG Ab, can be of prognostic value in AITD and psoriasis.

Navigating patient journey in early diagnosis of lung cancer in India.

Lung cancer (LC) is one of the leading causes of cancer deaths worldwide. In India, the incidence of LC is increasing rapidly, and a majority of the patients are diagnosed at advanced stages of the disease when treatment is less likely to be effective. Recent therapeutic developments have significantly improved survival outcomes in patients with LC. Prompt specialist referral remains critical for early diagnosis for improved patient survival. In the Indian scenario, distinguishing LC from benign and endemic medical conditions such as tuberculosis can pose a challenge. Hence, awareness regarding the red flags-signs and symptoms that warrant further investigations and referral-is vital. This review is an effort toward encouraging general physicians to maintain a high index of clinical suspicion for those at risk of developing LC and assisting them in refering patients with concerning symptoms to specialists or multidisciplinary teams as early as possible.

Clinical management of stage III non-small cell lung cancer in India: An expert consensus statement.

Non-small cell lung cancer (NSCLC) is considered the most common type of lung cancer (>80% of all lung cancers); patients are often diagnosed at advanced stages of the disease. The management of NSCLC is considered challenging owing to variations in size, an extension of the tumors, involvement patterns, and classification. Although adequate literature and guidelines are available on the management of NSCLC in several countries, an Indian perspective on stage III NSCLC management is lacking. We used the modified Delphi approach to form consensus statements. A thorough literature search was done. The authors then convened and deliberated over published literature, available guidelines, and clinical judgment. Recommendation statements were formed for different clinical scenarios. These statements were sent as a form of survey to other oncologists, and their responses were recorded and mentioned. Evidence-based statements were formed for diagnosing and managing stage III NSCLC. These recommendation statements cover various aspects-surgical, radiation, and medical treatment in various clinical scenarios including adjuvant, neoadjuvant, and consolidation therapies.

A relaxed implant bed: implants placed after two weeks of osteotomy with immediate loading: a one year clinical trial.

A waiting period of 2 weeks after osteotomy increases the surrounding tissue activity to its maximum level as collagen formation and neoangiogenesis represent a relaxed and acceptable implant bed configuration. The aim of the present study was a clinical and radiologic evaluation of early osteotomy with implant placement delayed for 2 weeks with immediate loading in the anterior and premolar region with minimally invasive approach. Seven GS II implants (Osstem) were placed in 6 patients. Osteotomy was done followed by flap closure without placement of the implant. After waiting for approximately 2 weeks, implant placement was done, which was loaded immediately with provisional crown in implant protected occlusion. It was replaced by definitive restoration after 6-8 weeks, which was considered baseline. Implant stability and marginal bone levels were assessed with clinical and radiologic parameters at baseline, 6- and 12-month intervals. None of the implants were found mobile during the 1-year period. The average mean marginal bone loss was 0.4 mm over the 1-year follow-up period. In the present study, early osteotomy with delayed implant placement showed negligible crestal bone loss with no mobility.

Liver profile in COVID-19: a meta-analysis.

BACKGROUND: Few studies have been performed to investigate multiorgan failure occurring with extrapulmonary symptoms like diarrhea, anorexia, and vomiting. There has been no attempt at a systematic review on this major health issue. Hence, in this study, a meta-analysis was undertaken to quantify the overall risk of liver damage in COVID-19 patients and also find the overall variation in risk outcome. MATERIALS AND METHODS: A meta-analysis was carried out on the findings of four published studies that were related to the albumin, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels of COVID-19 patients. The pooled mean for each of these three measurements was estimated by using a random-effects model. RESULTS: The pooled means for albumin, AST, and ALT in COVID-19 patients were 38.84 g/L [95% confidence interval (CI): 35.83-41.86], 27.28 IU/L (95% CI: 18.30-36.26), and 24.44 IU/L (95% CI: 15.73-33.15) respectively. There was a high degree of divergence among the studies, with the index of heterogeneity being more than 90%. CONCLUSION: The ALT and albumin pooled means were reported to be within the normal range; however, the pooled mean of the serum AST level was found to be high in COVID-19 patients. The pooled means reported in this study can be useful for working out the degree of liver damage in COVID-19 patients.

Flavonoids, alkaloids and terpenoids: a new hope for the treatment of diabetes mellitus.

Diabetes mellitus is a metabolic syndrome characterized by a hyperglycemic state and multi-organ failure. Millions of people worldwide are suffering from this deadly disease taking a hit on their pocket and mental health in the name of its treatment. Modern medical practices with new technological advancements and discoveries have made revolutionary changes in the treatment. But, unfortunately, Glucose-lowering drugs used have many accompanying effects such as chronic vascular disease, renal malfunction, liver disease and, many skin problems. These complications have made us think about alternative treatments for diabetes with minimum or no side effects. Nowadays, in addition to modern medicine, herbal treatment has been suggested to treat diabetes mellitus. These herbal medicines contain biological macromolecules such as flavonoids, Terpenoids, glycosides, and alkaloids, which show versatile anti-diabetic effects. These phytochemicals are generally considered safe, and naturally occurring compounds have a potential role in preventing or controlling diabetes mellitus. The underlying mechanism of their anti-diabetic effects includes improvement in insulin secretion, decrease in insulin resistance, enhanced liver glycogen synthesis, antioxidant and anti-inflammatory activities. In this review, we have focused on the mechanism of various phytochemicals targeting hyperglycemia and its underlying pathogenesis.

Evaluation of fracture resistance in class II tooth cavity using different techniques.

It is of interest to evaluate the fracture resistance of endodontically and non-endodontically treated teeth with class II cavity using different techniques and materials. Endodontic access cavities were prepared with the diamond fissure bur following the MOD cavity preparations,. The root canals preparation was done followed by obturation using the single cone obturation technique. Later all the samples were embedded in acrylic resin blocks and divided into 8 groups; Group 1: -Intact teeth (Control), Group 2: - MOD (unfilled), Group 3: - MOD restored with composite resin (3M FILTEK P-60 packable), Group 4: - MOD restored with Cention N (Ivoclar Vivadent), Group 5: - 10 mm fiber-post with composite resin, Group 6: - 5mm fiber post with composite resin, Group 7: - Ribbond on the occlusal and composite resin, and Group 8: - Horizontal fiber post with composite resin. Later all samples were subjected for fracture resistance testing using Universal Testing Machine. The mean fracture resistance of Control (513.2 N), Unfilled (60.2N), composite resin (221 N), cention N (88.9 N), 10 mm fiber post (271.4 N), 5 mm fiber post (245 N), Ribbond (456.4N), and horizontal fiber post (338.1N) was found. The fracture resistance values are statistically significant between each group. Best fracture resistance was found to be of intact teeth followed by ribbond on the occlusal surface after endodontic treatment and least fracture resistance of MOD unfilled. Thus, ribbond method is good for the occlusal of teeth compared to other materials for fracture resistance.

IHC versus FISH versus NGS to detect ALK gene rearrangement in NSCLC: all questions answered?

AIMS: Anaplastic lymphoma kinase (ALK) rearranged non-small cell lung carcinoma (NSCLC) is a distinct molecular subtype and rapid approval of ALK tyrosine kinase inhibitors (TKIs) has necessitated rapid and sensitive diagnostic modalities for the detection of this alteration. Gene rearrangements can be identified using many techniques including fluorescence in situ hybridisation (FISH), reverse transcriptase-PCR, next-generation sequencing (NGS) and immunohistochemistry (IHC) for fusion oncoprotein expression. We aimed to determine the concordance between IHC, FISH and NGS for ALK biomarker detection, and determine differences in sensitivity, and survival outcomes. METHODS: We analysed the concordance between IHC using D5F3 monoclonal antibody, FISH (break-apart) and NGS using a custom panel containing 71 different ALK variants. RESULTS: Among 71 cases included in this study, FISH was evaluable in 58 cases. The concordance of ALK IHC with FISH was 75.9% and that with NGS was 84.5%. The sensitivities of FISH and NGS were 75.6% and 87.5%, respectively. The median progression-free survival of ALK IHC-positive and FISH-negative group was 5.5 months and that of both positive was 9.97 months. CONCLUSION: Although NGS offers a better throughput and visualisation, IHC still remains the quintessential screening tool in upfront diagnosis of ALK rearranged NSCLC.

Spontaneous pulmonary arterial embolization: A rare complication of the silicon-based peripherally inserted central venous catheter (PICC).

Peripherally inserted central catheters (PICC) are widely used in oncology for administration of chemotherapy. However, sometimes there may be complications associated with them such as infections, thrombosis and rarely fracture of catheter and embolization of the catheter fragments. Here we report a case of 59-year old gentleman with locally advanced carcinoma of head of pancreas, who had spontaneous fracture of a silicon based PICC and later migration of the catheter fragment through the heart and further into the right pulmonary arterial system. The embolized catheter fragment was retrieved through a vascular snare from the right femoral venous route. This case highlights the fact that silicon PICCs are fragile and have a high risk of spontaneous dislodgement and should be replaced by better alternative polyurethane PICCs.