Operational Metrics for the ELAINE 2 Study Combining a Traditional Approach With a Just-in-TIME Model.

PURPOSE: There are numerous barriers to enrollment in oncology biomarker-driven studies. METHODS: The ELAINE 2 study (ClinicalTrials.gov identifier: NCT04432454) is an open-label phase 2 study of lasofoxifene combined with abemaciclib in patients with advanced or metastatic estrogen receptor-positive/human epidermal growth factor receptor 2-negative breast cancer with an ESR1 mutation. ELAINE 2 opened clinical sites by using a Traditional approach, which activated a site before patient identification, and the Tempus TIME Trial network, which opened a site only after identifying an eligible patient. This manuscript presents the operational metrics comparing the Traditional and TIME Trial site data. RESULTS: The study enrolled patients over 34 weeks and 16 sites (six Traditional and 10 TIME Trial) participated. Duration for full clinical trial agreement execution for Traditional sites and TIME Trial sites averaged 200.5 (range, 142-257) and 7.6 days (range, 2-14), respectively. Institutional review board approval time for Traditional sites and TIME Trial sites was 27.5 (range, 12-71) and 3.0 days (range, 1-12), respectively. Duration from study activation to first consent was 33.3 (range, 18-58) and 8.8 days (range, 1-35) for Traditional and TIME Trial sites, respectively. The first patient on study was at a TIME Trial site 115 days before a Traditional site and the first seven patients enrolled were at TIME Trial sites. Traditional sites consented 23 and enrolled 16 patients, while TIME Trial sites consented 16 and enrolled 13. The trial enrolled 29 patients in 8.5 months with the anticipated enrollment duration being 12-18 months. CONCLUSION: The TIME Trial network opened earlier and enrolled the first study patients. These results demonstrate that the Just-in-TIME model, along with a Traditional model, can improve enrollment in biomarker-driven studies.

Cellular reprogramming with ATOH1, GFI1, and POU4F3 implicate epigenetic changes and cell-cell signaling as obstacles to hair cell regeneration in mature mammals.

Reprogramming of the cochlea with hair-cell-specific transcription factors such as ATOH1 has been proposed as a potential therapeutic strategy for hearing loss. ATOH1 expression in the developing cochlea can efficiently induce hair cell regeneration but the efficiency of hair cell reprogramming declines rapidly as the cochlea matures. We developed Cre-inducible mice to compare hair cell reprogramming with ATOH1 alone or in combination with two other hair cell transcription factors, GFI1 and POU4F3. In newborn mice, all transcription factor combinations tested produced large numbers of cells with the morphology of hair cells and rudimentary mechanotransduction properties. However, 1 week later, only a combination of ATOH1, GFI1 and POU4F3 could reprogram non-sensory cells of the cochlea to a hair cell fate, and these new cells were less mature than cells generated by reprogramming 1 week earlier. We used scRNA-seq and combined scRNA-seq and ATAC-seq to suggest at least two impediments to hair cell reprogramming in older animals. First, hair cell gene loci become less epigenetically accessible in non-sensory cells of the cochlea with increasing age. Second, signaling from hair cells to supporting cells, including Notch signaling, can prevent reprogramming of many supporting cells to hair cells, even with three hair cell transcription factors. Our results shed light on the molecular barriers that must be overcome to promote hair cell regeneration in the adult cochlea.

Multiparameter Optimization of Naphthyridine Derivatives as Selective α5-GABAA Receptor Negative Allosteric Modulators.

The discovery and characterization of novel naphthyridine derivatives with selective α5-GABAAR negative allosteric modulator (NAM) activity are disclosed. Utilizing a scaffold-hopping strategy, fused [6 + 6] bicyclic scaffolds were designed and synthesized. Among these, 1,6-naphthyridinones were identified as potent and selective α5-GABAAR NAMs with metabolic stability, cardiac safety, and beneficial intellectual property (IP) issues. Relocation of the oxo acceptor function and subsequent modulation of the physicochemical properties resulted in novel 1,6-naphthyridines with improved profile, combining good potency, selectivity, ADME, and safety properties. Besides this, compound 20, having the most balanced profile, provided in vivo proof of concept (POC) for the new scaffold in two animal models of cognitive impairment associated with schizophrenia (CIAS).

Glial-Specific Deletion of Med12 Results in Rapid Hearing Loss via Degradation of the Stria Vascularis.

Mediator protein complex subunit 12 (Med12) is a core component of the basal transcriptional apparatus and plays a critical role in the development of many tissues. Mutations in Med12 are associated with X-linked intellectual disability syndromes and hearing loss; however, its role in nervous system function remains undefined. Here, we show that temporal conditional deletion of Med12 in astrocytes in the adult CNS results in region-specific alterations in astrocyte morphology. Surprisingly, behavioral studies revealed rapid hearing loss after adult deletion of Med12 that was confirmed by a complete abrogation of auditory brainstem responses. Cellular analysis of the cochlea revealed degeneration of the stria vascularis, in conjunction with disorganization of basal cells adjacent to the spiral ligament and downregulation of key cell adhesion proteins. Physiologic analysis revealed early changes in endocochlear potential, consistent with strial-specific defects. Together, our studies reveal that Med12 regulates auditory function in the adult by preserving the structural integrity of the stria vascularis.SIGNIFICANCE STATEMENT Mutations in Mediator protein complex subunit 12 (Med12) are associated with X-linked intellectual disability syndromes and hearing loss. Using temporal-conditional genetic approaches in CNS glia, we found that loss of Med12 results in severe hearing loss in adult animals through rapid degeneration of the stria vascularis. Our study describes the first animal model that recapitulates hearing loss identified in Med12-related disorders and provides a new system in which to examine the underlying cellular and molecular mechanisms of Med12 function in the adult nervous system.

Transcription Factor Reprogramming in the Inner Ear: Turning on Cell Fate Switches to Regenerate Sensory Hair Cells.

Non-mammalian vertebrates can restore their auditory and vestibular hair cells naturally by triggering the regeneration of adjacent supporting cells. The transcription factor ATOH1 is a key regulator of hair cell development and regeneration in the inner ear. Following the death of hair cells, supporting cells upregulate ATOH1 and give rise to new hair cells. However, in the mature mammalian cochlea, such natural regeneration of hair cells is largely absent. Transcription factor reprogramming has been used in many tissues to convert one cell type into another, with the long-term hope of achieving tissue regeneration. Reprogramming transcription factors work by altering the transcriptomic and epigenetic landscapes in a target cell, resulting in a fate change to the desired cell type. Several studies have shown that ATOH1 is capable of reprogramming cochlear non-sensory tissue into cells resembling hair cells in young animals. However, the reprogramming ability of ATOH1 is lost with age, implying that the potency of individual hair cell-specific transcription factors may be reduced or lost over time by mechanisms that are still not clear. To circumvent this, combinations of key hair cell transcription factors have been used to promote hair cell regeneration in older animals. In this review, we summarize recent findings that have identified and studied these reprogramming factor combinations for hair cell regeneration. Finally, we discuss the important questions that emerge from these findings, particularly the feasibility of therapeutic strategies using reprogramming factors to restore human hearing in the future.

Nodular syphilitic scleritis: a rare and forgotten entity.

Ocular manifestations of syphilis are usually seen in the secondary or tertiary stages of the disease, which is a nonspecific inflammatory response. We report a case of unilateral nodular scleritis in a patient with late latent syphilis, which resolved with intravenous crystalline penicillin for 2 weeks, topical fluorometholone, and tobramycin eye drops for 3 weeks.

Placental lipid metabolism in preeclampsia.

OBJECTIVES: The current study examines the placental and maternal lipid profile and expression of genes involved in placental lipid metabolism in women with preeclampsia. METHODS: The current study includes normotensive control women (n = 40) and women with preeclampsia (n = 39). Preeclampsia women were further classified into women delivering at term preeclampsia (T-PE; n = 15) and preterm preeclampsia (PT-PE; n = 24). RESULTS: There were no significant differences in maternal lipid profile between the T-PE and normotensive control groups. Maternal plasma VLDL (P < 0.05) and ratios of total cholesterol : HDL (P < 0.05), atherogenic index [log (triglycerides/HDL)] (P < 0.01) and apolipoprotein B : apolipoprotein A (P < 0.05) were higher in the PT-PE group as compared with the normotensive control group. Placental total cholesterol and HDL levels were higher (P < 0.05) in the T-PE as compared with the normotensive control group. Higher placental triglycerides (P < 0.05) were observed in PT-PE group compared with T-PE group. Placental mRNA levels of peroxisome proliferator activated receptor α, carnitine palmitoyl transferase-1, cluster of differentiation 36 and lipoprotein lipases were lower (P < 0.05) in the PT-PE than normotensive control group. A negative association of mRNA levels of peroxisome proliferator activated receptor α (r = -0.246, P = 0.032; r = -0.308, P = 0.007, respectively), carnitine palmitoyl transferase-1 (r = -0.292, P = 0.011; r = -0.366, P = 0.001), lipoprotein lipases (r = -0.296, P = 0.010; r = -0.254, P = 0.028) with SBP and DBP was observed. There was a positive association of placental triglycerides (r = 0.244, P = 0.031) with DBP. CONCLUSION: Women with preeclampsia exhibit higher lipid : lipoprotein ratios suggesting an atherogenic state particularly in women delivering preterm. Lower expression of genes involved in placental fatty acid oxidation and transport was also observed in preeclampsia.

Leptin as a predictive marker for metabolic syndrome.

Metabolic syndrome poses a major threat on human health affecting the quality of life. Adipose tissue is an important organ which plays a crucial role in the pathogenesis of metabolic syndrome. Adipocytokines secreted by the adipose tissue plays a critical role in storage, food intake, energy expenditure, lipid and glucose metabolism. Leptin is primarily involved in regulating food intake, body weight and energy homeostasis through neuroendocrine functions. Contemporary research suggests that leptin also influences insulin sensitivity and lipid metabolism. High leptin concentrations are directly associated with the obesity subsequent development of metabolic disease sequelae such as insulin resistance, type 2 diabetes and cardiovascular diseases. Elucidation of the mechanism of action of leptin would help to develop novel therapeutic approaches for there metabolic disorders like obesity and diabetes. This review provides an updated 'state-of-the-art' about the leptin and its role in the pathophysiology of metabolic syndrome at the molecular level.

Increased levels of superoxide dismutase suppress meiotic segregation errors in aging oocytes.

The risk of meiotic segregation errors increases dramatically during a woman's thirties, a phenomenon known as the maternal age effect. In addition, several lines of evidence indicate that meiotic cohesion deteriorates as oocytes age. One mechanism that may contribute to age-induced loss of cohesion is oxidative damage. In support of this model, we recently reported (Perkins et al. in Proc Natl Acad Sci U S A 113(44):E6823-E6830, 2016) that the knockdown of the reactive oxygen species (ROS)-scavenging enzyme, superoxide dismutase (SOD), during meiotic prophase causes premature loss of arm cohesion and segregation errors in Drosophila oocytes. If age-dependent oxidative damage causes meiotic segregation errors, then the expression of extra SOD1 (cytosolic/nuclear) or SOD2 (mitochondrial) in oocytes may attenuate this effect. To test this hypothesis, we generated flies that contain a UAS-controlled EMPTY, SOD1, or SOD2 cassette and induced expression using a Gal4 driver that turns on during meiotic prophase. We then compared the fidelity of chromosome segregation in aged and non-aged Drosophila oocytes for all three genotypes. As expected, p{EMPTY} oocytes subjected to aging exhibited a significant increase in nondisjunction (NDJ) compared with non-aged oocytes. In contrast, the magnitude of age-dependent NDJ was significantly reduced when expression of extra SOD1 or SOD2 was induced during prophase. Our findings support the hypothesis that a major factor underlying the maternal age effect in humans is age-induced oxidative damage that results in premature loss of meiotic cohesion. Moreover, our work raises the exciting possibility that antioxidant supplementation may provide a preventative strategy to reduce the risk of meiotic segregation errors in older women.

Imperatorin ameliorates lipopolysaccharide induced memory deficit by mitigating proinflammatory cytokines, oxidative stress and modulating brain-derived neurotropic factor.

BACKGROUND: Lipopolysaccharide (LPS), an endotoxin from the outer membrane of Gram negative bacteria has been reported to cause neuroinflammation and learning and memory deficits. There are reports describing the beneficial effects of Imperatorin (IMP), a naturally occurring furanocoumarin in central nervous system (CNS) disorders such as anxiety and epilepsy. OBJECTIVE: In the current study, we investigated whether IMP protects against LPS mediated memory deficits and neuroinflammation. METHODS: Mice pretreated with IMP (5, 10 mg/kg po) were administered LPS (250 µg/kg ip) for 7 days. Memory was evaluated in the Morris water maze (MWM) and Y maze. The mice were euthanised and different biochemical assessments were carried out to measure oxidative stress and acetyl choline esterase (AChE). Further, evaluation of proinflammatory cytokines such as tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) levels and brain derived neurotrophic factor (BDNF) in hippocampus and cortex of brain were performed. RESULTS: LPS administration caused poor memory retention in both, MWM and Y maze, and caused distinct oxidative stress since decrease in superoxide dismutase (SOD), reduced glutathione (GSH) levels and increased lipid peroxidation were observed. Also, a significant rise was observed in the levels of AChE. Moreover, a rise in TNF-α and IL-6 levels and depleted levels of BDNF were noted. IMP pretreatment reversed LPS induced behavioral and memory disturbances and significantly decreased the oxidative stress and AChE levels. It also reduced TNF-α and IL-6 levels and caused a significant upregulation of BDNF levels. CONCLUSION: Present study highlights the potential neuroprotective role of IMP against LPS mediated cognitive impairment and neuroinflammation.

Adiponectin: A potential therapeutic target for metabolic syndrome.

Adiponectin is an important adipocytokine secreted chiefly by fat containing adipocytes, and plays a crucial role in glucose and lipid metabolism, inflammation and oxidative stress. Alterations in adiponectin levels have been shown to directly affect lipid and glucose metabolism that further increase the synthesis of lipids, free fatty acids and inflammatory cytokines. Changes in adiponectin levels also contribute to insulin resistance, obesity, cardiovascular diseases and type 2 diabetes. In the present review, we provide a comprehensive evaluation of the role of adiponectin and its molecular mechanisms in metabolic syndrome. Clinical improvement in adiponectin levels have been shown to positively modulate lipid and glucose metabolism, thus further substantiating its role in regulation of lipid and glucose metabolism. Currently adiponectin is being investigated as a potential therapeutic target for metabolic syndrome, although more research is required to understand the underlying mechanisms controlling adiponectin levels, including dietary and lifestyle interventions, that may target adiponectin as a therapeutic intervention in metabolic syndrome.

In vitro antiglycating effect and in vivo neuroprotective activity of Trigonelline in d-galactose induced cognitive impairment.

BACKGROUND: Alzheimer's disease (AD) is characterized by amyloid beta (Aß) plaques, neurofibrillary tangles (NFTs) and cognitive impairment. Literature cites the role of advanced glycation end products (AGEs) in AD due to increased cytotoxicity via oxidative stress. d-galactose (d-gal) induced amnesia stimulates Aß overproduction via increased oxidative stress and AGEs. Trigonelline (TRG), a naturally occurring alkaloid has been reported to have neuroprotective and antidiabetic properties. METHODS: Present study assessed the protective effect of TRG against in vitro AGEs formation. Since chronic administration of d-gal increases AGEs, we subsequently investigated the neuroprotective role of TRG (50 and 100 mg/kg as per body weight) against d-gal induced amnesia. Mice were subcutaneously (sc) injected with d-gal (150 mg/kg) for 6 weeks. Behavioral assessments in Morris water maze (MWM) and Y-maze were performed, followed by biochemical estimations to deduce the probable mechanism of action. RESULTS: In vitro experiments demonstrated that TRG stalled early and late AGEs formation. Chronic d-gal administration significantly impaired cognitive performance in MWM and Y maze, caused marked oxidative damage, elevated the AGEs levels and significantly increased the acetylcholinesterase levels as compared to sham group. TRG (50 and 100 mg/kg) treatment significantly ameliorated cognitive performance, reversed the oxidative damage, decreased AGE levels and caused significant decline in acetylcholine esterase levels as compared to d-gal group. CONCLUSION: Present study highlights the neuroprotective role of TRG against d-gal induced amnesia due to the antioxidant, antiglycative and anticholinesterase properties.

Trigonelline insulates against oxidative stress, proinflammatory cytokines and restores BDNF levels in lipopolysaccharide induced cognitive impairment in adult mice.

Neuroinflammation is said to play a pivotal role in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). Trigonelline (TRG) is a naturally occurring alkaloid, commonly isolated from fenugreek and coffee beans. In the present study, we investigated whether TRG exerts neuroprotective action against LPS mediated cognitive impairment. Mice pretreated with TRG (50 and 100 mg/kg po) were administered with LPS (250 µg/kg ip) for 7 days. Memory was assessed in the Morris water maze (MWM) and Y maze. LPS administration caused poor memory retention in MWM and Y maze paradigms, and resulted in marked oxidative stress as evidenced by decrease in superoxide dismutase (SOD), reduced glutathione (GSH) levels and increased lipid peroxidation in the hippocampus and cortex. Cholinergic involvement during neuroinflammation was evaluated by measuring levels of acetylcholinesterase (AChE) enzyme. TRG treatment at both the doses reversed LPS induced behavioral and memory disturbances, significantly decreased the oxidative stress and AChE levels in both the hippocampus and cortex. LPS administration also elevated the tumour necrosis factor (TNF-α) and interleukin -6 (IL-6) levels, whereas brain derived neurotrophic factor (BDNF) levels were significantly depleted. TRG pretreatment led to decreased TNF-α and IL-6 levels and caused a significant upregulation of BDNF levels. In conclusion, present study highlights the promising neuroprotective role of TRG against LPS mediated cognitive impairment which could be attributed to reduced oxidative stress, inhibition of proinflammatory cytokines and restoration of BDNF levels.

Synthesis, DNA binding and in-vitro cytotoxicity studies on novel bis-pyrazoles.

A new series of bis-pyrazoles 6a-t were synthesized from 3,5-dimethyl pyrazole using sequential approach. All these compounds were characterized by IR, 1H NMR, 13C NMR and mass spectral data. The interaction of newly synthesized bis-pyrazoles with DNA was investigated through molecular docking and absorption spectroscopic technique. Among all bis-pyrazoles compounds, the 6h compound showed lower conformational energy through in silico analysis. The interaction of each molecule in this series 6a-t with the various concentrations of DNA was examined through the UV-visible spectroscopic studies. The UV-visible spectroscopy studies on the specific binding of compound 6a, 6b, 6g, 6h, 6d, 6i, 6k, 6n, 6s with DNA have exhibited spectral shifts and the results were discussed. In further the compounds 6a-t were subjected to the in-vitro cytotoxicity studies against human pancreatic adenocarcinoma, human non-small cell lung carcinoma cell lines. Among the screened compounds, N-(3-isopropoxy-1-isopropyl-4-(3,5-dimethyl-1H-pyrazol-1-yl)-1H-pyrazol-5-yl)cyclobutane carboxamide and N-(5'-Isopropoxy-2'-isopropyl-3,5-dimethyl-2'H-[1,4'] bipyrazolyl-3'-yl)-dimethane sulfonamide were found as lead molecules since they have exhibited promising activity against both the cancer cell lines used in this study, whereas the compounds 4-(trifluoromethyl)-N-(3-isopropoxy-1-isopropyl-4-(3,5-dimethyl-2H-pyrrol-2-yl)-1H-pyrazol-5-yl)benzamide and 2,6-difluoro-N-(3-isopropoxy-1-isopropyl-4-(3,5-dimethyl-2H-pyrrol-2-yl)-1H-pyrazol-5-yl) benzamide were found to be active against the pancreatic cell line only. Rest all the other compounds were found to exhibit moderate to good activity towards both the cell lines.

Attenuation of glycation-induced multiple protein modifications by Indian antidiabetic plant extracts.

CONTEXT: Protein glycation is the major contributing factor in the development of diabetic complications. The antiglycation potential of medicinal plants provides a promising opportunity as complementary interventions for complications. OBJECTIVE: To investigate the antiglycation potential of 19 medicinal plants extracts using albumin by estimating different indicators: (1) glycation (early and late), (2) albumin oxidation, and (3) amyloid aggregation. MATERIALS AND METHODS: The effect of aqueous plant extracts (1% w/v) on protein glycation was assessed by incubating albumin (10 mg/mL) with fructose (250 mM) for 4 days. Degree of protein glycation in the absence and presence of plant extracts was assessed by estimating fructosamine, advanced glycation end products (AGEs), carbonyls, free thiol group and ß-amyloid aggregation. RESULTS: Petroselinum crispum, Boerhavia diffusa, Terminalia chebula, Swertia chirayita and Glycyrrhiza glabra showed significant antiglycating activity. P. crispum and A. barbadensis inhibited the carbonyl stress and protected the thiol group from oxidative damage. There was significant correlation between protein thiols and amyloid inhibition (R = -.69, p < .001). CONCLUSION: P. crispum, B. diffusa and T. chebula had the most potent antiglycation activity. These plant exerted noticeable antiglycation activity at different glycation modifications of albumin. These findings are important for identifying plants with potential to combat diabetic complications.

Blastomycosis-Like Pyoderma- A Rare Case Report.

Blastomycosis-like pyoderma is a rare, cutaneous bacterial infection of skin, seen in malnourished individuals, in a poor state of health and manifests as vegetating skin lesions. It is an unusual tissue reaction possibly to bacterial infection, the most common organism being Staphylococcus aureus. This case report is of a 35-year-old male who presented with thick verrucous surfaced plaques and papules on trunk and extremities since 2 months. Investigations revealed anaemia with hypochromasia, neutrophilic leucocytosis, hypo-proteinemia and hypo-albuminemia with reversal of A/G ratio. Pathergy test was negative. Pus on Gram's stain showed plenty of pus cells, and negative for AFB and fungal stain. On culture of pus grew Coagulase negative staphylococcus species. Biopsy showed acanthosis of epidermis with moderate lymphocytic infiltrates in dermis and focally a few neutrophils and histiocytes. Patient fulfilled the criteria for diagnosis of blastomycosis like pyoderma viz., presentation of large verrucous plaques with pustules and ulcers with elevated border, histologically neutrophilic infiltration and growth of one pathogenic bacterium on culture. Patient responded to long-term cefotaxime therapy.

Palonosetron and granisetron in postoperative nausea vomiting: A randomized double-blind prospective study.

BACKGROUND: Postoperative nausea and vomiting (PONV) is a common occurrence after laparoscopic surgeries. A number of pharmacological agents (antihistamines, butyrophenones, dopamine receptor antagonists) have been tried of which the 5-hydroxytryptamine type 3 receptor antagonists are devoid of most side effects and highly effective in prevention and treatment of PONV. Thus, we evaluated the effectiveness of granisetron and palonosetron in prevention of PONV after laparoscopic surgeries under general anesthesia. AIMS: We conducted a study to evaluate the effectiveness of granisetron and palonosetron, to compare the duration of action and side effects if any, in patients undergoing elective laparoscopic surgery under general anesthesia. SETTINGS AND DESIGN: This was a prospective, randomized, double-blinded, comparative study. Sixty patients (18-65 years of age) of the American Society of Anesthesiologists Grade I and II undergoing elective laparoscopic surgeries were considered. MATERIALS AND METHODS: They were randomly allocated into one of the two groups (Group G and Group P) of thirty patients each. Group G received injection granisetron 0.05 mg/kg; Group P received injection palonosetron 1.5 mcg/kg intravenous bolus 30 min before the induction of anesthesia. STATISTICAL TESTS: All statistical analyses were performed using the SPSS® statistical package version 18.0 (Chicago: SPSS Inc). Two independent sample t-test was used for quantitative data, and the χ2 or Fisher's exact test was used for qualitative data. A difference was regarded as statistically significant at a P < 0.05. RESULTS: The need for rescue antiemetic was significantly lower in Group P in the 24-72 h postoperative period (ρ - 0.007). The PONV score was significantly less in Group P in the same period (ρ - 0.008). The incidence of side effects was statistically insignificant in both the groups (ρ - 0.999). CONCLUSION: Prophylactic therapy with palonosetron is more effective than granisetron in the prevention of PONV after laparoscopic surgeries under general anesthesia.

Palmoplantar Dermatoses- A Clinical Study of 300 Cases.

INTRODUCTION: Dermatoses affecting palms and soles are among the most difficult of all dermatological therapeutic problems. Many previous studies have focused on the specific diseases of palmoplantar dermatoses. However, none of them have included a comprehensive study of palmoplantar dermatoses. AIMS: To study the epidemiological aspects like age distribution, sex distribution, the dermatoses affecting the palms & soles and the frequency of involvement of palms, soles or both palms & soles, in patient with palmoplantar dermatoses. MATERIALS AND METHODS: This cross sectional study was conducted in the Department of Dermatology between October 2011 to September 2013. First 300 cases attending the department of dermatology primarily with complaints pertaining to palms and soles were enrolled in the study. After taking consent a detailed history and clinical examination pertaining to the aim of the study was recorded and analysed, which included inspection of morphology and distribution of lesions and palpation of any swelling. Direct microscopic examination of scrapings, wet mounted with 10% potassium hydroxide was done for cases with scaly lesions. Those who had a pustule, gram staining was done. Patch testing using Indian Standard Battery Series was done for those cases of eczema. A sample for biopsy was taken when diagnosis could not be arrived clinically, and subjected to histopathological examination. RESULTS: In our study of 300 patients with palmoplantar dermatoses, 164 were females and 136 were males, the ratio observed being 1.2:1. The peak incidence was found in the age group 21-30 years, with 41 females (25%) and 35 males (25.7%). Most frequently affected individuals in this study were housewives (30%). The most common five diseases of palmoplantar dermatoses were palmoplantar psoriasis (20.7%), moniliasis (19%), palmoplantar hyperhidrosis (7%), keratolysis exfoliativa (6%) and pitted keratolysis (6%). Majority of patients had involvement of both palms and soles (44.3%) as compared to patients with involvement of only palm (28%) and only sole (27.3%). The commonest palmoplantar dermatoses with only palm involvement was keratolysis exfoliativa (16.7%), with only sole involvement was moniliasis (41%) and with both palms and soles involvement was palmoplantar psoriasis (41.4%). Associated nail changes were seen in 80 cases (26.6%), with maximum incidence in palmoplantar psoriasis (62.5%). Associated dermatological conditions were observed in 43 patients (14.3%). CONCLUSION: Palmoplantar dermatoses are frequently encount-ered in the dermatologic field. Further investigation with a wider and larger population is necessary to understand the epidemiology, based on which accurate diagnosis and proper treatment could be achieved.