ASSOCIATION OF MPV AND RDW WITH DISEASE ACTIVITY IN PATIENT WITH RHEUMATOID ARTHRITIS.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder characterized by inflammation of the synovial joints. Disease activity assessment plays a crucial role in guiding treatment decisions and monitoring disease progression in RA patients. Thus, the current study examines the association between Mean Platelet Volume (MPV), Red Cell Distribution Width (RDW), and disease activity in RA patients. A total of 100 patients were included following the inclusion and exclusion criteria. All participants underwent physical examination and laboratory tests. Disease activity was assessed using the Disease Activity Score 28 (DAS28). The cut-off levels for RDW and MPV were 14.8 and 11.25, respectively. However, a significant association was observed between RDW levels and DAS28, indicating that the group with RDW ≤14.8% displayed higher DAS compared to the RDW >14.8% group. Also, MPV levels did not exhibited statistically significant variations. RDW levels did not show significant disparities among patients with different comorbidities. There is a significant correlation exists between RDW and disease activity in RA exists. Moreover, RDW can be utilized in clinical settings to monitor disease activity effectively. Since RDW is routinely included in standard blood tests, it is cost-effective and more convenient for treating RA cases.

TRIGLYCERIDE - GLUCOSE INDEX, REMNANT CHOLESTEROL AND COMMON CAROTID ARTERY INTIMA-MEDIA THICKNESS AS AN ATHEROSCLEROTIC MARKER IN ISCHEMIC STROKE PATIENTS.

Ischemic stroke (IS) is a major global health concern, often resulting from atherosclerosis and insulin resistance (IR). The triglyceride-glucose index (TyG index), remnant cholesterol (RC), and common artery intima-media thickness (CIMT) are potential markers for assessing atherosclerosis and cardiovascular risk in IS patients. A cross-sectional study was conducted to investigate the association between TyG index, RC, CIMT, and IS in adult patients recruited from a hospital. Demographic, clinical, and laboratory data were collected, and statistical analysis was performed. The study included 50 participants with a balanced gender distribution and a mean age of 57.64 years. Laboratory characteristics showed notable values, and CIMT > 0.6 mm was associated with higher NIH Stroke Scale scores. RC exhibited significant correlations with age, CIMT, lipid profile, and TyG index. The study highlights the potential of TyG index, RC, and CIMT as atherosclerotic markers in IS patients. Favorable prognostic outcomes were observed, emphasizing the importance of early diagnosis and management to improve patient outcomes.

Correction: An Observational Study of Hearing Loss Among Menopausal Women.

[This corrects the article DOI: 10.1007/s12070-023-04121-5.].

Ent Manifestations in Sculptors of South Chennai, India: A Cross Sectional Observational Study.

Despite the National Occupational Safety and Legislation Act 2020's implementation, reports of workplace accidents are rising in India. Various ear, nose, and throat conditions have been linked to a wide range of physico-chemical variables. Due to a lack of training, inadequate knowledge, a lack of awareness of occupational health and safety risks, or a lack of accessibility to or use of personal protective equipment (PPE), sculptors are frequently exposed to a variety of physical, compound and unplanned risks, chemical, and accidental hazards. The study aimed to assess the various ear, nose and throat manifestations like noise induced hearing loss, occupational rhinitis and non-infectious pharyngitis among the sculptors working in the southern part of Chennai. This observational study was performed in a total of 110 sculptors. Demographic data like age, education, duration of occupation, use of PPE like face mask, ear plug during work hours, whether sculpting is a family occupation or first generation sculptor. A detailed history and thorough ENT examination was performed with pure tone audiometry (PTA), diagnostic nasal endoscopy (DNE) and videolaryngoscopy (VLS). If any problem is detected they will be treated accordingly. Most of them (70%) were in the age group of 21-40 years but 71% of them are sculptors for more than 15 years which infers introduction to the occupation at an early age. The reason for this could be more than 80% of them possessed the heritage of sculpting as their family occupation. Duration of occupation was significantly associated with chronic rhinitis (P value was 0.002) and NIHL (P value was 0.002) whereas education and use of PPE like face mask or ear plugs were not associated with ENT manifestations. This study focuses on the sculptors' working habits, their ignorance of safety precautions, and an assessment of the numerous ENT ailments. These manifestations showed a strong correlation to exposure time. To prevent the issues from becoming more severe, regular medical monitoring is required for early detection and intervention.

An Observational Study of Hearing Loss Among Menopausal Women.

Senile deafness and hearing loss in adults over 50 are major public health issues as a result of the population's ageing demographic. Menopausal women tend to develop hearing loss, while no clear link has been found between the two. The purpose of this study was to determine how menopause and diabetes mellitus affects hearing loss. We assessed 158 menopausal women in total. Pure Tone Audiometry and HbA1c levels was measured, along with appropriate clinical history and examination. The association between those levels and hearing was researched by chi-square test. There were 158 study participants. Mean age of the study population was 50.5 (± 2.49) years. Onset and duration of hard of hearing was assessed in 41 patients (25.9%). 33% (N = 53) of the patients had history of Diabetes mellitus, of which 52.8% offered history of the disease for more than or equal to five years. On audiological assessment, 74.1% had no hearing loss (N = 117), 4.4% had unilateral sensorineural hearing loss (N = 7) and 21.5% had bilateral sensorineural hearing loss (N = 34). Statistics show that hearing loss is statistically connected with ageing and poor glycemic management. With chi square values of 9.629 and P value 0.002 found a significant correlation between ageing and hearing loss. Poor glycemic control is significantly associated with hearing loss with a chi-square value of 4.304 and P value 0.038. Poor glycemic control and menopause is found to be strongly associated with sensorineural hearing loss. Further prospective, hormonal studies including larger population is recommended.

Palladium-Catalyzed Cascade Endo-dig Cycloisomerization and Olefination with Alkenes to Access Fused Oxatricyclic Compounds.

A novel cascade Pd(II)-catalyzed endo-dig cycloisomerization and olefination reaction of 2-benzyl-3-alkynyl chromones with activated/unactivated alkenes has been developed for the synthesis of fused oxatricyclic compounds. This concise one-pot synthetic approach was applied to the difunctionalization of unbiased alkynes based on 2-benzyl-3-(alkynyl)-4H-chromen-4-one via O-attack endo-dig cycloisomerization, followed by olefination with both activated and unactivated alkenes.

Case Series - Pediatric Tracheostomy for Upper Airway Obstruction.

Certain congenital craniofacial malformations can cause upper airway obstruction. Due to neurological involvement, these craniofacial deformities with upper airway blockage frequently require tracheostomy. Children who need weeks or months of continuous ventilator assistance require tracheostomies, which improve pulmonary toilet and decrease laryngotracheal lesions such subglottic stenosis and tracheomalacia. In this case report we will be discussing about two patients who underwent Pediatric tracheostomy for Pierre Robin sequence and supraglottic stenosis in our institute. This paper emphasizes on some of the rare causes of pediatric upper airway obstruction - Pierre Robin sequence and supraglottic stenosis. Also the importance of tracheostomy procedure, which is the gold standard for management of upper airway obstruction in patients who are not responding to conservative management is emphasized. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-023-03892-1.

Evaluating the Outcomes of Closed Reduction of Different Types of Nasal Bone Fractures.

This study was conducted to evaluate the outcomes of closed reduction of different types of nasal bone fractures depending on time between onset of injury and reduction and comparing the outcomes of early closed reduction (within 6 h) of nasal bone fracture with late closed reduction (after 2 weeks). A hospital based Prospective cohort type of study was conducted among cases of nasal bone fracture attending the outpatient department of Otorhinolaryngology at Chettinad Hospital and Research Institute, Chennai during the months of August 2021 to January 2022. A total of 54 participants were included in the study. Primary outcome was to assess the effectiveness of closed reduction of different types of nasal bone fractures postoperatively. The second objective was to compare the outcomes of early closed reduction (within 6 h) of nasal bone fracture with late closed reduction (after 2 weeks). Using chi square test, the association of factors such as age, sex, mode of injury, external framework deformity, type of fracture and treatment was analyzed with outcome measures such as post op degree of deviation, arch irregularity, malalignment, bony irregularity, bony displacement, olfactory disturbances and result. We analyzed the sample data statistically and measured the outcomes which showed that post operatively after undergoing closed reduction, some degree of deviation was present in 17(31.48./.), arch irregularity present in 12(22.2./.), malalignment in 11(20.37./.), bony irregularity in 24(44.44./.), bony displacement in 19(35.19./.), olfactory disturbances in 2(3.70./.). Comparing the outcome factors between early and late reduction, we found that the outcome was better in early closed reduction when compared with late closed reduction. Among the 54 patients studied, the results of closed reduction were found to be excellent in 27(50./.), Fair in 16(29.63./.), Good in 10(18.52./.) and poor in 1(1.85./.) We could thus conclude from this study that early closed reduction of nasal bone fracture gave better results than a late closed reduction in terms of post operative deformity, arch irregularity, malalignment, bony irregularity, bony displacement and olfactory disturbances.

The Comparison of the Anti-inflammatory Efficacy of Phytochemical Extracts in Punica granatum and Lawsonia inermis Among Patients Diagnosed With Chronic Periodontitis.

Introduction The oral cavity is the gateway to the human body. Periodontitis is a common inflammatory condition affecting the oral cavity and a known etiological cause of tissue destruction, discomfort, and halitosis. Pomegranate (Punica granatum) and henna (Lawsonia inermis) are herbs known to mankind from time immemorial whose extracts are proven to fight inflammation. The current study was done to evaluate the phytochemical anti-inflammatory efficacy of Punica and Lawsonia in patients with chronic periodontitis and test the potency of herbal mouthwashes in fighting the inflammatory condition affecting the oral cavity using distilled water as a control group. Materials and methods A double-blinded randomized control trial was conducted on 60 patients who were recruited and divided into three groups, in which 20 patients were prescribed with pomegranate (Punica: n=20) mouthwash and 20 patients with henna (Lawsonia: n=20) mouthwash along with distilled water (n=20). All patients were randomly allocated using the coin toss method and advised to use the prescribed mouthwash for a period of two weeks. Unstimulated saliva was collected before using the mouthwash, and salivary enzymes such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) and their levels were assessed spectrometrically using the infrared spectrophotoscopy (IFSC) method. Each patient was assigned a mouthwash and recalled after two weeks. Unstimulated saliva was again collected, and salivary activity levels of enzymes AST, ALT, and LDH were analyzed after using mouthwash in a similar method as done before. Later on, the salivary levels of enzymes AST, ALT, and LDH were compared before and after the usage of mouthwashes. Statistical significance was seen in the salivary enzymatic activity of AST, ALT, and LDH before and after using Punica and Lawsonia mouthwashes due to their potent phytochemical action in fighting inflammation. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) 22 (IBM SPSS Statistics, Armonk, NY). The Shapiro-Wilk test was used to determine the normality and significance; intragroup comparison was done using the Wilcoxon signed-rank test and Mann-Whitney U test. Intergroup comparison was done using the Kruskal-Wallis test. Results Punica patients had much lower levels of salivary AST and ALT (p<0.001) and a decrease in LDH (p=0.002) after the usage of mouthwash for a period of two weeks. Also, patients using Lawsonia as herbal mouthwash had reduction in the values of AST (p=0.001) and LDH (p=0.003) and prominent reduction in ALT (p<0.001) after a period of two weeks. But in the case of patients using distilled water, there was an increase in the salivary enzymatic activity of AST and ALT, which was statistically significant (p<0.001), and LDH (p=0.006) depicting the disease progression even after using mouthwash for the given time period of two weeks. Conclusion This study demonstrated that both Punica and Lawsonia were effective in reducing the inflammation in patients diagnosed with chronic periodontitis. However, when intergroup comparison was done, the anti-inflammatory efficacy was superior in Punica with significant reduction in the parameters such as of AST, ALT, and LDH when compared to Lawsonia owing to its potent phytochemical constituency in cutting down the inflammation. Hence, Punica can be used as an implicated effective anti-inflammatory herbal mouthwash.

Varied Clinical Presentations of Allergic Fungal Rhinosinusitis-A Case Series.

Fungal sinusitis is broadly classified into invasive and non invasive types. Invasive type presents with fungal hyphae within the mucosa, submucosa, bone, or blood vessels of the paranasal sinuses and includes Acute Invasive Fungal Sinusitis, Acute Fulminant, Chronic Invasive Fungal Sinusitis, Chronic Granulomatous Fungal Sinusitis. Invasive forms of fungal rhinosinusitis are rare and confined to groups of patients who are immunocompromised (Key in Fungal rhinosinusitis). Noninvasive type shows absence of fungal hyphae within the mucosa paranasal sinuses. It includes Allergic Fungal rhinosinusitis, Fungus Ball (fungus mycetoma). The study was performed on a total of 30 patients, in Department of Otorhinolaryngology, at our hospital after getting approved by the Instituitional Human Ethical Committee. We selected 30 patients diagnosed with allergic fungal sinusitis and studied their varied clinical presentations and treatment for a period of 1 year. It was a prospective case series type of study. Patients who presented with symptoms of allergic fungal rhinosinusitis were included. Patients who were referred with complaints of proptosis, diplopia were also included to rule out allergic fungal rhinosinusitis and its complications. Patients diagnosed with chronic granulomatous infection of nose and invasive fungal sinusitis were excluded. Evaluation of patients involved a detailed case history followed by clinical examination and radiologic investigation. After getting proper consent, we did a study of 30 patients who presented to our outpatient department with complaints of sinusitis. Our study included 12 male and 18 female patients. Among these patients, all of them had complaints of frequent allergic rhinosinusitis, nose block, facial heaviness. 12 among them had olfactory disturbances, reduced perception of smell. 4 patients presented with visual disturbances and proptosis which subsided after endoscopic sinus surgery was done.24 among these patients had presence of allergic fungal mucin in their nasal secretions and 10 patients had history of associated atopy and asthma and elevated Ig E levels. And 20 of these patients showed high eosinophil counts. All these patients in our case series were under the age group 22-70 years. These patients were treated with a course of nasal sprays and preoperative steroids in case of extensive polyposis and were taken up for functional endoscopic sinus surgery. Polypoidal mucosa was removed, diseased tissue was cleared, sinus blockage was released and fungal mucin/tissue bits were sent for histopathological analysis, KOH mount and fungal culture. This study included a series of cases which showed a wide range of the various clinical presentations that occur in cases of allergic fungal rhinosinusitis, its diagnosis and treatment. The advantage of this study was we had analyzed a good number of cases with varied presentations. Since AFRS is closely related with EMRS, CRS a proper clinical, radiological and immunological evaluation of the cases help in knowing the correct diagnosis and treatment.

Synthesis and thermomechanical properties of bioplastics and biocomposites: a systematic review.

Materials research relating to bio-based polymers and composites has become the order of the day and several types of research are being undertaken on these materials. This is mainly due to the belief in the ability of these polymers and composites to serve as potential alternatives for synthetic polymers and fiber-reinforced composites and to mitigate problems pertaining to environmental pollution. A majority of synthetic fibers and polymers in the market today are developed from nonrenewable petroleum-based materials. These have the potential to harm the natural biodiversity of the environment. On the other hand, the use of bioplastics and biocomposites is supported by a few facts such as low cost, lesser energy consumption during production, and notable mechanical and thermal characteristics. The usage of bio-based fibers and polymers in the manufacture of biocomposites in numerous applications greatly enhance the sustainability by eradicating the problem of waste generation. Considering all the above points, the current review focuses on the synthesis and characterization of bioplastics and biocomposites. An elaborate discussion on the mechanical and thermal properties of these materials has also been made. In addition, this review comprehensively discusses the applications, challenges, and prospects of bioplastics and biocomposites.

Adsorption isotherm, kinetics and response surface methodology optimization of cadmium (Cd) removal from aqueous solution by chitosan biopolymers from cephalopod waste.

The present investigation was aimed to explore the cadmium removal efficiency, mechanism and characterization of Chitosan biopolymers from cephalopods waste. The extracted chitosan has showed good yield of 32% and with high minerals, ash and moisture content. In the Fourier-transform infrared spectroscopy (FT-IR) analysis multiple active functional groups of Amine, Amine, Hydroxyl were found between 612 and 3424 cm-1 and the sugar signals such as N-acetyl glucosamine (GlcNAc) and H-1 [GlcN (H-1D), GlcNAc (H-1A)] were identified in Chitosan by 1H Nuclear Magnetic Resonance (NMR). The Crystalline, rough surface, micropores characters were observed in Chitosan surface by Scanning Electron Microscope (SEM) analysis and the pores played a key role in adsorption process. The Cd ions removal was performed by batch experiment and the results were revealed that the pH, temperature, time and dosage highly influenced the process and the optimum condition was discovered through RSM for pH 7, temperature 42.5 °C, time 220 min and dosage of sorbent 1 g/L respectively. The kinetics models of the Cd removal were carried out and the results revealed that the Pseudo-second order is more suitable and fit for removal than Pseudo-first order model. Chitosan surface characters and functional groups played a big role in adsorption process and Chitosan can be alternative eco-friendly, low cost and highly efficient sorbent for heavy metal removal in effluent treatment plants.

Spatial variation of covid-19 morbidity status and identification of risk zone in Tamil Nadu (India) during first wave.

COVID-19 is a pandemic disease caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). The study area, Tamilnadu, is a southern state in India. The present study demonstrates the significance of mapping in identifying the risk zones of COVID-19 disease by taking a study of COVID-19 cases in Tamilnadu state. The main objective of the study was to identify the risk zone of COVID-19 disease in the first wave of Tamilnadu through geospatial mapping. Data on COVID-19 cases collected during March 2020 to March 2021 month wise in all 37 districts (unit area) of Tamilnadu in two-month interval wise was analysed. The study is based on secondary sources from respective office in Tamilnadu. Z-score techniques were used for standardizing data. Correlation analysis provided a measure of correlation between COVID-19 and working population. Location Quotient analysis aided the identification of COVID-19 risk zones in Tamilnadu. Present study indicates tertiary workers are more vulnerable to COVID-19 disease.

Palladium-Catalyzed Chemo- and Regiocontrolled Tandem Cyclization/Cross-Coupling of 2-Benzyl-3-alkynyl Chromones with Aryl Iodides for the Synthesis of 4H-Furo[3,2-c]chromenes and Xanthones.

A novel Pd-catalyzed chemo- and regiocontrolled tandem cyclization/cross-coupling reaction of 3-alkynyl chromone with aryl iodide was developed for the synthesis of 4H-furo[3,2-c]chromenes and xanthones. The difunctionalization of alkynes through O-attack/5-exo-dig and C-attack/6-endo-dig cyclization was reported by this rare approach, which was selectively controlled by the addition of KF or a bidentate phosphine ligand. A one-pot tandem process was demonstrated directly from γ-alkynyl-1,3-diketone for this method.

Assessment of Effects on Prolonged Usage of Face Mask by ENT Professionals During Covid-19 Pandemic.

The protection efficacy of face masks during this covid 19 pandemic has been well documented. The changes in human nasal functions after wearing facemask for prolonged period is not known. The aim of this study is to determine the effects of prolonged usage of facemask by ENT professionals during covid 19 pandemic. It is a cross sectional study conducted in department of ENT in Chettinad Hospital and Research Institute, Kelambakkam. A self-constructed questionnaire containing 21 queries regarding the effects of prolonged use of face mask, after being analysed by the experts of our institution were distributed to 124 ENT professionals all over India. People who are ENT by professionals can participate in this study. Participation is voluntary. Study period was from March 2020 to December 2020. All answered questionnaires were sent for statistical analysis. 63.71% experienced difficulty in breathing while wearing face mask, 37.10% experienced dry nose, 46.77% experienced dry mouth. The most common modality of prevention in an OPD setup was face mask with face shield (31.45%). About 80.65% people believed there are side effects due to wearing mask. Since facemasks are essential to protect us from COVID-19, certain strategies can be followed to reduce the discomfort due to its prolonged usage such as encouraging nasal breathing, taking short breaks from wearing mask in a safe environment and to maintain hydration.

Pd-Catalyzed and ligand-enabled alkene difunctionalization via unactivated C-H bond functionalization.

Palladium-catalyzed and ligand-enabled C-H functionalization methods have emerged as a powerful approach for the preparation of therapeutically important motifs and complex natural products. Olefins, owing to their natural abundance, have been extensively employed for the formation of C-C and C-X bonds and the generation of various heterocycles. Traditionally, activated as well as starting materials with preinstalled functional groups, and also halide substrates under transition metal catalysis, have been employed for olefin difunctionalization. However, strategies for employing unactivated C-H bond functionalization to achieve alkene difunctionalization have rarely been explored. A possible solution to this challenge is the application of bulky ligands which enhances the reductive elimination pathway and inhibits ß-hydride elimination to selectively yield difunctionalized alkene products. This feature article summarizes the utilization of unreactive C-H bonds in the Pd-catalyzed and ligand-enabled difunctionalization of alkenes.

Intravascular papillary endothelial hyperplasia of the cavernous sinus-A rare occurrence.

Intravascular papillary endothelial hyperplasia (IPEH) is a benign, reactive proliferation of endothelial cells within areas of thrombus. It most commonly occurs in the skin and subcutaneous tissue, with less than 40 cases reported in intracranial location. Ours is the first case report from India of IPEH in the cavernous sinus. A 45-year-old male presented with headache and decreased visual acuity. Magnetic resonance imaging (MRI) revealed a well-defined, homogeneously contrast-enhancing mass in the cavernous sinus. Postoperatively, examination of tissue showed organizing thrombus within the vessel wall along with delicate, acellular, pseudopapillary cores. The fibrin-rich connective tissue of these showed blue staining with Masson's trichrome stain. These were lined by a single layer of endothelial cells without evidence of atypia; no nuclear pleomorphism, hyperchromasia, atypical mitosis, or areas of necrosis were seen. Hence, it was diagnosed to be IPEH. Follow-up MRI revealed no residual disease and the patient is disease-free at 8 months. Recognition of this entity by pathologic examination is important to rule out angiosarcoma. Gross total resection is curative. Residual lesions have the potential for recurrence, requiring adjuvant therapy.

Synthesis, biological evaluation, and correlation of cytotoxicity versus redox potential of 1,4-naphthoquinone derivatives.

A series of 1,4-naphthoquinone derivatives of lawsone (1), 6-hydroxy-1,4-naphthoquinone (2), and juglone (3) were synthesized by alkylation, acylation, and sulfonylation reactions. The yields of lawsone derivatives 1a-1k (type A), 6-hydroxy-1,4-naphthoquinone derivatives 2a-2j (type B), and juglone derivatives 3a-3h (type C) were 52-99%, 53-96%, and 28-95%, respectively. All compounds were tested in vitro for the cytotoxicity against human oral epidermoid carcinoma (KB) and cervix epithelioid carcinoma (HeLa) cells and their structure-activity relationship was studied. Compound 3c was found to be most potent in KB cell line (IC50 = 1.39 µM). Some compounds were evaluated for DNA topoisomerase I inhibition. Compounds 2c, 3, 3a, and 3d showed topoisomerase inhibition activity with IC50 values of 8.3-91 µM. Standard redox potentials (E°) of all naphthoquinones in phosphate buffer at pH 7.2 were examined by means of cyclic voltammetry. A definite correlation has been found between the redox potentials and inhibitory effects of type A compounds.

Dataset for compression ignition engine fuelled with corn oil methyl ester biodiesel.

The present data study deals with the experimental analysis of performance, emission and combustion characteristics of CI engine fuelled with corn oil methyl ester biodiesel blend as alternative fuel. A two-step trans esterification process is used to produce the biodiesel. Furthermore, a characteristics study was carried out on the extracted corn oil methyl ester biodiesel blends over conventional fuel. Three different fuel blends namely B10, B20 and B30 were chosen and the performance, emission and combustion characteristics of these are compared to that of conventional diesel fuel. Eddy current dynamometer is used load the engine from no load to maximum load condition. Using AVL DiGAS 444 N gas analyser and AVL 346 smoke meter the emissions and smoke opacity of the fuel blends and diesel were measured respectively. The experimental performance, emission and combustion data's were presented.

Design, synthesis and optimization of bis-amide derivatives as CSF1R inhibitors.

Signaling via the receptor tyrosine kinase CSF1R is thought to play an important role in recruitment and differentiation of tumor-associated macrophages (TAMs). TAMs play pro-tumorigenic roles, including the suppression of anti-tumor immune response, promotion of angiogenesis and tumor cell metastasis. Because of the role of this signaling pathway in the tumor microenvironment, several small molecule CSF1R kinase inhibitors are undergoing clinical evaluation for cancer therapy, either as a single agent or in combination with other cancer therapies, including immune checkpoint inhibitors. Herein we describe our lead optimization effort that resulted in the identification of a potent, cellular active and orally bioavailable bis-amide CSF1R inhibitor. Docking and biochemical analysis allowed the removal of a metabolically labile and poorly permeable methyl piperazine group from an early lead compound. Optimization led to improved metabolic stability and Caco2 permeability, which in turn resulted in good oral bioavailability in mice.