Systematic review and meta-analysis of surgical approaches for improving airway stability in infants with Robin sequence: Evaluating complications and outcomes.

The purpose of this systematic review and meta-analysis was to determine the most effective and least morbid surgical technique for relieving retroglossal airway obstruction in infants with Robin sequence (RS). The study adhered to PRISMA guidelines and included 25 studies (24 cohorts and one case series) that investigated interventions for airway improvement, including conservative measures, tongue-lip adhesion (TLA), mandibular distraction osteogenesis (MDO), and tracheostomy. The primary outcome variable was complication rate, while predictor variable was the use of interventions for airway improvement. Results showed that conservative measures were the preferred initial management strategy in most studies, while TLA was recommended for infants with mild obstruction, and MDO or tracheostomy was reserved for severe cases. Only complications could be analysed via meta-analysis due to data heterogeneity, revealing that tracheostomy had a summary odds ratio of 5.39 in favour of TLA, while MDO had a ratio of 2.8 over TLA, and the complication rates were similar between MDO and tracheostomy. If conservative measures fail, the study recommends mandibular distraction as the preferable technique for stable airway improvement. If the infant is unsuitable for distraction, tongue-lip adhesion may serve as an alternative, while tracheostomy should be reserved for cases of severe multi-level obstruction. The authors propose that large-scale, multicentre trials comparing long-term outcomes are required to establish definitive guidelines.

Proxy consultations for severe mental illnesses: An exploratory cross-sectional study from a tertiary care hospital.

BACKGROUND: Non-adherence to medication leading to a break in continuity of care poses significant challenges in severe mental illness (SMI), leading to poor outcomes. In India, proxy consultation, wherein caregivers consult on behalf of patients, is a commonly adopted but insufficiently researched area to address these challenges. AIMS: To explore the extent of proxy consultation in outpatient care of persons with SMI and investigate its sociodemographic and clinical correlates. METHODOLOGY: In a tertiary care psychiatry outpatient setting, we conducted a cross-sectional study involving 374 caregivers of persons with SMI (Schizophrenia, Bipolar and related disorders). Descriptive statistics and univariate logistic regression were performed to examine correlates' relationships with proxy consultation. RESULTS: Proxy consultation prevalence was 43% in the past 1 year. Compared with 18 to 30 years, middle-aged patients aged 31 to 40, 41 to 50 and 51 to 60 years had twofold, threefold and sixfold increased chances of proxy consultation, respectively. Being illiterate had six times higher odds than graduates, three times and two times if they studied till primary and secondary education. Early age of onset was associated with three times higher chances of proxy consultation compared to the onset of illness in adulthood. On the contrary, male gender and upper and middle socioeconomic status decreased the chances of proxy consultation by 40%. Financial difficulties (n = 72, 45%) and patients' unwillingness to visit outpatients (n = 44, 27.5%) were the most commonly cited reasons for proxy consultation. CONCLUSION: Proxy consultations are relatively common, driven by many social, economic, patient-related, pragmatic and practical factors. In formulating community care policies for persons with SMI, the primary imperative should be to conduct additional research, deepening our understanding of proxy consultations. Additionally, it is essential to be mindful of the diverse issues associated with proxy consultations during the formulation process.

Enriched characteristics of poultry collagen over other sources of collagen and its extraction methods: A review.

Collagen is the most abundant protein in animals and is extensively studied for its structural and thermal stability, biocompatibility, and healing properties which enables them to be widely applied in various fields. Collagen extracted from poultry sources have shown improved structural stability and reduced risk of triggering allergic responses and transmitting animal diseases onto humans. Furthermore, poultry collagen is widely accepted by consumers of diverse beliefs in comparison to collagen extracted from bovine and porcine sources. The review aims to compare different sources of collagen, focusing on the various beneficial characteristics of poultry collagen over the other sources. Moreover, the review explains various pre-treatment and extraction methods of poultry collagen and its versatile applications in different industrial sectors.

Insights into the emergence and evolution of monkeypox virus: Historical perspectives, epidemiology, genetic diversity, transmission, and preventative measures.

In 2022, just before the COVID-19 pandemic ended, many countries noticed a viral monkeypox outbreak. Monkeypox virus, a zoonotic pathogen, causes a febrile illness in humans and resembles smallpox. Prevention strategies encompass vaccination, strict infection control measures, and avoiding contact with infected persons. As monkeypox and related poxviruses continue to pose challenges, ongoing surveillance, early diagnosis, prompt isolation, and effective control measures are crucial for limiting transmission and mitigating the impact of outbreaks on public health. This review provides valuable insights into the evolution of the monkeypox virus and its various modes of transmission, including postmortem transmission, and offers an overall perspective on the guidelines issued by the Government of India to prevent and effectively control the spread of this disease.

Prospects of liquid biopsy in the prognosis and clinical management of gastrointestinal cancers.

Gastrointestinal (GI) cancers account for one-fourth of the global cancer incidence and are incriminated to cause one-third of cancer-related deaths. GI cancer includes esophageal, gastric, liver, pancreatic, and colorectal cancers, mostly diagnosed at advanced stages due to a lack of accurate markers for early stages. The invasiveness of diagnostic methods like colonoscopy for solid biopsy reduces patient compliance as it cannot be frequently used to screen patients. Therefore, minimally invasive approaches like liquid biopsy may be explored for screening and early identification of gastrointestinal cancers. Liquid biopsy involves the qualitative and quantitative determination of certain cancer-specific biomarkers in body fluids such as blood, serum, saliva, and urine to predict disease progression, therapeutic tolerance, toxicities, and recurrence by evaluating minimal residual disease and its correlation with other clinical features. In this review, we deliberate upon various tumor-specific cellular and molecular entities such as circulating tumor cells (CTCs), tumor-educated platelets (TEPs), circulating tumor DNA (ctDNA), cell-free DNA (cfDNA), exosomes, and exosome-derived biomolecules and cite recent advances pertaining to their use in predicting disease progression, therapy response, or risk of relapse. We also discuss the technical challenges associated with translating liquid biopsy into clinical settings for various clinical applications in gastrointestinal cancers.

Determinants of health literacy and its impact on glycemic control among women with gestational diabetes mellitus in a tertiary care hospital, Puducherry - A cross-sectional analytical study.

BACKGROUND: Health literacy is vital during pregnancy, as maternal health knowledge and behavior have a significant impact on the health of both mother and child. Hence, this study aimed to assess the health literacy status of pregnant women diagnosed with gestational diabetes mellitus (GDM), as well as its associated factors and impact on glycemic control. MATERIALS AND METHODS: The facility-based Cross-sectional analytical study was conducted among 200 pregnant women with GDM in a tertiary care hospital. The eligible participants were consecutively selected for the study. The study was conducted from September 2022 to March 2023. A validated semi-structured questionnaire, the Health Literacy Questionnaire (HLQ) for GDM, was used to measure health literacy status. Stata V.17 software was used for data analysis. RESULTS: Out of 200 pregnant women with GDM, the mean (SD) age of the participants is 29.5 (±5.5) years. It was observed that 164 (82%) of the participants had adequate health literacy, whereas 36 (18%) had inadequate health literacy about Gestational Diabetes. Adequate health literacy (HL) was observed among 88.5% of women with controlled blood sugar and 55.1% of women with uncontrolled blood sugar. Results of multivariate logistic regression analysis revealed that pregnant mothers' educational status (PR: 1.8; 95% CI: 1.2-2.5) and glycemic control (PR: 1.4; 95% CI (1.2-1.7) were associated with adequate HL. CONCLUSIONS: In conclusion, this study supports the association between adequate HL and glycemic control in pregnant women with GDM. Addressing this gap is essential for healthcare officials and planners to implement programs that promote women's HL during pregnancy, with a focus on low-educated groups.

Plausible role of INPP4A dysregulation in idiopathic pulmonary fibrosis.

INPP4A has been shown to be involved in the regulation of cell proliferation and apoptosis of multiple cell types including fibroblasts. Previous reports from our group have demonstrated the role of inositol polyphosphate 4-phosphatase Type I A (INPP4A) in these functions. Though existing evidences suggest a critical role for INPP4A in the maintenance of lung homeostasis, its role in chronic lung diseases is relatively under explored. In the current study, we made an attempt to understand the regulation of INPP4A in idiopathic pulmonary fibrosis (IPF). Through integration of relevant INPP4A gene expression data from public repositories with our results from in vitro experiments and mouse models, we show that INPP4A is altered in IPF. Interestingly, the direction of the change is dependent both on the disease stage and the region of the lung used. INPP4A was found to be upregulated when analyzed in lung sample representative of the whole lung, but was downregulated in the fibrotic regions of the lung. Similarly, INPP4A was found to be high, compared to controls, only in the early stage of the disease. Though the observed increase in INPP4A was found to be negatively correlated to physiological indices, FVC, and DLCO, of lung function, treatment with anti-INPP4A antibody worsened the condition in bleomycin treated mice. These contrasting results taken together are suggestive of a nuanced regulation of INPP4A in IPF which is dependent on the disease stage, cellular state and extent of fibrosis in the lung region being analyzed.

Factors influencing access to psychiatric care among persons with psychosis living in a rural community in south India.

BACKGROUND: A substantial proportion of persons with psychosis (PWP) remain untreated in the community across the world. Factors that preclude them from accessing psychiatric treatment are poorly studied. In this study, we explored the factors that prevented persons with schizophrenia and their caregivers from accessing psychiatric treatment using an interview schedule specifically developed for this purpose. METHODS: We identified individuals with schizophrenia and related disorders who had never accessed psychiatric treatment. We interviewed 67 such individuals and their family members using a validated tool, the Schedule of Factors Influencing Access to Treatment (SOFIAc) and analysed the data using descriptive statistics. RESULTS: The M (SD) number of factors reported to preclude individuals with psychosis and families from seeking psychiatric treatment was 10 (3.32). No PWP/family reported any single factor as the sole reason for not accessing treatment. Distance to the nearest psychiatric centre (97%), PWP's/family members' knowledge and attitude towards symptoms of psychosis and treatment (92.5%), financial problems (91%), lack of insight and active resistance to efforts towards treatment (86.6%), lack of support from the family (83.6%) and family issues and dynamics (79.1%) were reported to be the commonest factors that precluded them from accessing psychiatric treatment. CONCLUSIONS: The reason for individuals with psychosis and their family members not accessing psychiatric treatment was invariably multifactorial, involving, on average, 10 factors. Programmes that target the reduction of the treatment gap should be cognizant of the multifactorial nature of the challenge of reaching psychiatric treatment for persons with psychoses.

Implications of Low-concentration Polymer on the Physical Stability of Glassy Griseofulvin: Role of the Segmental Mobility.

Crystallization of amorphous pharmaceutical solids are widely reported to be affected by the addition of polymer, while the underlying mechanism require deep study. Herein, crystal growth behaviors of glassy griseofulvin (GSF) doped with various 1% w/w polymer were systematically studied. From the molecular structure, GSF cannot form the hydrogen bonding interactions with the selected polymer poly(vinyl acetate), polyvinyl pyrrolidone (PVP), 60:40 vinyl pyrrolidone-vinyl acetate copolymer (PVP/VA 64), and poly(ethylene oxide) (PEO). 1% w/w polymer exhibited weak or no detectable effects on the glass transition temperature (Tg) of GSF. However, crystal growth rates of GSF was altered from 4.27-fold increase to 2.57-fold decrease at 8 ℃ below Tg of GSF. Interestingly, the ability to accelerate and inhibit the growth rates of GSF crystals correlated well with Tg of polymer, indicating the controlling role of segmental mobility of polymer. Moreover, ring-banded growth of GSF was observed in the polymer-doped systems. Normal compact bulk and ring-banded crystals of GSF were both characterized as the thermodynamically stable form I. More importantly, formation of ring-banded crystals of GSF can significantly weaken the inhibitory effects of polymer on the crystallization of glassy GSF.

Enhancing grid resiliency in distributed energy systems through a comprehensive review and comparative analysis of islanding detection methods.

Reduction of fossil fuel usage, clean energy supply, and dependability are all major benefits of integrating distributed energy resources (DER) with electrical utility grid (UG). Nevertheless, there are difficulties with this integration, most notably accidental islanding that puts worker and equipment safety at risk. Islanding detection methods (IDMs) play a critical role in resolving this problem. All IDMs are thoroughly evaluated in this work, which divides them into two categories: local approaches that rely on distributed generation (DG) side monitoring and remote approaches that make use of communication infrastructure. The study offers a comparative evaluation to help choose the most efficient and applicable IDM, supporting well-informed decision-making for the safe and dependable operation of distributed energy systems within electrical distribution networks. IDMs are evaluated based on NDZ outcomes, detection duration, power quality impact, multi-DG operation, suitability, X/R ratio reliance, and efficient functioning.

Structural basis of DNA crossover capture by Escherichia coli DNA gyrase.

DNA supercoiling must be precisely regulated by topoisomerases to prevent DNA entanglement. The interaction of type IIA DNA topoisomerases with two DNA molecules, enabling the transport of one duplex through the transient double-stranded break of the other, remains elusive owing to structures derived solely from single linear duplex DNAs lacking topological constraints. Using cryo-electron microscopy, we solved the structure of Escherichia coli DNA gyrase bound to a negatively supercoiled minicircle DNA. We show how DNA gyrase captures a DNA crossover, revealing both conserved molecular grooves that accommodate the DNA helices. Together with molecular tweezer experiments, the structure shows that the DNA crossover is of positive chirality, reconciling the binding step of gyrase-mediated DNA relaxation and supercoiling in a single structure.

Phytochemical analysis and antioxidant potential of Mondia whitei and Guibourtia tessmannii against H2O2-induced cytotoxicity in PC3 cells.

The management of oxidative stress-related disorders has garnered significant interest, particularly in the exploration of medicinal plants possessing potent antioxidant activities. This study was undertaken to evaluate the antioxidant activity of Mondia whitei (MW) and Guibourtia tessmannii (GT) against H2O2-induced cytotoxicity in PC3 cells. The phytochemical composition of MW and GT was determined by GC-MS analysis. Total phenolic (TP) and total flavonoid (TF) contents were quantified by Folin Ciocalteu and AlCl3 methods, respectively. The antioxidant potential of the extracts was determined using the DPPH and ABTS+ radicals scavenging method, as well as cupric and ferric reducing capacity assay. Moreover, all phytocompounds were docked against acetylcholinesterase (AChE) and glutathione S-transferase (GST) using ArgusLab, and results were analyzed using the BIOVIA Discovery Studio Visualizer 2021 client. MW and GT comprised 20 and 22 compounds, respectively. GT exhibited higher TP and TF contents (210.70 ± 12.7; 12.61 ± 1.3 GAE/g DW) compared to MW (132.59 ± 12.59; 5.53 ± 1.3 mg of GAE/g DW). Both MW and GT demonstrated substantial antioxidant activity, with GT proving to be more effective in preventing H2O2-induced cytotoxicity. For instance, MW and GT significantly (p < .001) increased the DPPH, ABTS+, and cupric activity, compared with the H2O2 group. All compounds identified in MW and GT exhibited a strong binding affinity against AChE and GST. Drug likeness and toxicity of all phytocompounds were under the acceptable norms of Lipinski's rule. In conclusion, these plants could be effective candidates for the management/treatment of oxidative stress-related disorders.Communicated by Ramaswamy H. Sarma.

Implementing the practice of early skin-to-skin contact among infants ≥35 weeks gestation born vaginally: a quality improvement study.

BACKGROUND: Early skin-to-skin contact (SSC) at birth has been shown to improve neonatal outcomes due to enhanced cardiorespiratory stability, thermoregulation and breastfeeding success. LOCAL PROBLEM: The practice of early SSC was virtually non-existent in our delivery room (DR). METHODS AND INTERVENTIONS: The study was conducted in a newly established tertiary care teaching hospital in Western Rajasthan, India. We aimed to improve the median duration of early SSC from 0 min to at least 60 min over 24 weeks in our DR. A quality improvement (QI) team was formed, and all inborn infants ≥35 weeks born vaginally from 9 March 2017 were included. Using the tools of point-of-care QI, we found the lack of standard operating procedure, lack of knowledge among nursing staff regarding early SSC, routine shifting of all infants to radiant warmer, the practice of prioritising birthweight documentation and vitamin K administration as the major hindrances to early SSC. Various change ideas were implemented and tested sequentially through multiple plan-do-study-act (PDSA) cycles to improve the duration of early SSC. Interventions included framing a written policy for SSC, sensitising the nursing staff and resident doctors, actively delaying the alternate priorities, making early SSC a shared responsibility among paediatricians, obstetricians, nursing staff and family members, and continuing SSC in the recovery area of the DR complex. RESULTS: The duration of early SSC increased from 0 to 67 min without any additional resources. The practice of SSC got well established in the system as reflected by a sustained improvement of 63 min and 72 min, respectively, at the end of 2 months and 4 years after study completion. CONCLUSION: Using the QI approach, we established and sustained the practice of early SSC for more than 60 min in our unit by using system analysis and testing change ideas in sequential PDSA cycles.

Antimalarial potential of Kerala Ayurvedic Water.

BACKGROUND OBJECTIVES: The persistent threat of drug resistant malaria demands new cures. Low prevalence of malaria in the Indian state of Kerala compared with other proximal states made us explore if there is any traditional practice in Kerala which may confer protection against malaria. In this context, our attention was drawn to 'Pathimugam' i.e., Ceasalpinia sappan whose heartwood is used to prepare a red aqueous extract which is a uniquely popular drink in Kerala. METHODS: Aqueous and methanolic extracts of various organs of C. sappan were prepared and tested against Plasmodium falciparum grown in vitro culture using SYBR Green-I assay. The cytotoxicity of active extracts/fractions was studied using mammalian HeLa cell line. in vivo efficacy was determined using P. berghei ANKA infected mice. RESULTS: The highest antiplasmodial activities in the alcoholic and aqueous extracts were observed in leaf methanolic extract (IC50 2 µg/ml) and heartwood aqueous extract (IC50 12.5 µg/ml). Ceasalpinia sappan extracts were equipotent against both chloroquine-sensitive Pf3D7 and resistant PfINDO strains and showed suppression of percentage parasitemia in P. berghei infected mice. Activity- guided chromatographic fractionation of aqueous wood extract led to the fortification of antiplasmodial activity (IC50 5 µg/ml). INTERPRETATION CONCLUSION: Our results establish the antiplasmodial potential of C. sappan and suggest that its regular use might have prophylactic or curative actions that may assist in keeping check on malaria in the Indian state of Kerala.

Modulation of Oxidative Stress and Glycemic Control in Diabetic Wistar Rats: The Therapeutic Potential of Theobroma cacao and Camellia sinensis Diets.

  Background Diabetes mellitus is a complex metabolic disorder characterized by oxidative stress and impaired glycemic control. This study investigates the therapeutic potential of Theobroma cacao and Camellia sinensis diets in diabetic Wistar rats and assesses their impact on oxidative stress markers and blood glucose levels. Methods  In this experiment, eight groups of six male Wistar rats (n = 12.5%), aged 8 to 12 weeks, were carefully set up to see how different treatments for diabetes and oxidative stress affected the two conditions. The random selection process was implemented to minimize any potential bias and ensure that the results of the study would be representative of the general population of Wistar rats. The groups were as follows: a nondiabetic control group (NDC) served as the baseline, while diabetes was induced in the alloxan monohydrate group (150 mg/kg). Another group was given the standard drug metformin (M, 100 mg/kg), and two control groups that did not have diabetes were given extracts of Theobroma cacao (TC, 340 mg/kg) and Camellia sinensis (CS, 200 mg/kg). Three groups of diabetic rats were given a mix of these treatments. Theobroma cacao and Camellia sinensis extracts were given at set doses (TC, 340 mg/kg; CS, 200 mg/kg), along with 150 mg/kg of a drug that causes diabetes. Over a 21-day period, oxidative stress parameters such as glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione reductase (GSHrd) levels, and blood glucose were carefully measured to check for signs of oxidative stress and diabetes progression Results Considerable differences in GSH levels were noted across the groups, with the highest GSH concentration found in the group treated with the inducing drug, while the lowest GSH levels were observed in the diabetic group that was administered both Theobroma cacao and Camellia sinensis (p < 0.001). MDA levels also varied, with the diabetic group treated with Theobroma cacao having the highest MDA concentration (3.54 ± 0.29 µmol/L) and the nondiabetic control group treated with Camellia sinensis exhibiting the lowest MDA levels (1.66 ± 0.08 µmol/L; p < 0.001). SOD activity was highest in the standard drug group and lowest in the diabetic group treated with Theobroma cacao. GSH activity was notably higher in the diabetic groups that received dietary interventions (p < 0.001). Blood glucose levels showed diverse responses, with the standard drug group experiencing a substantial reduction, while the inducing drug group exhibited a consistent increase. Conclusion The study highlights the significant impact of dietary interventions with Theobroma cacao and Camellia sinensis on oxidative stress markers and blood glucose regulation in diabetic Wistar rats. These findings suggest a potential role for these dietary components in mitigating oxidative stress and improving glycemic control in diabetes, although further research is warranted to elucidate the underlying mechanisms and clinical implications.

Design, synthesis, biological and computational screening of novel pyridine-based thiadiazole derivatives as prospective anti-inflammatory agents.

In this study, a novel series of pyridine-based thiadiazole derivatives (NTD1-NTD5) were synthesized as prospective anti-inflammatory agents by combining substituted carboxylic acid derivatives of 5-substituted-2-amino-1,3,4-thiadiazole with nicotinoyl isothiocyanate in the presence of acetone. The newly synthesized compounds were characterized by FTIR, 1H NMR, 13C NMR, and mass spectrometry. First, the compounds underwent rigorous in vivo testing for acute toxicity and anti-inflammatory activity and the results revealed that three compounds-NTD1, NTD2, and NTD3, displayed no acute toxicity and significant anti-inflammatory activity, surpassing the efficacy of the standard drug, diclofenac. Notably, NTD3, which featured benzoic acid substitution, emerged as the most potent anti-inflammatory agent among the screened compounds. To further validate these findings, an in silico docking study was carried out against COX-2 bound to diclofenac (PDB ID: 1pxx). The computational analysis demonstrated that NTD2, and NTD3, exhibited substantial binding affinity, with the lowest binding energies (-8.5 and -8.4, kcal/mol) compared to diclofenac (-8.4 kcal/mol). This alignment between in vivo and in silico data supported the robust anti-inflammatory potential of these derivatives. Moreover, molecular dynamics simulations were conducted, extending over 100 ns, to examine the dynamic interactions between the ligands and the target protein. The results solidified NTD3's position as a leading candidate, showing potent inhibitory activity through strong and sustained interactions, including stable hydrogen bond formations. This was further confirmed by RMSD values of 2-2.5 Å and 2-3Ǻ, reinforcing NTD3's potential as a useful anti-inflammatory agent. The drug likeness analysis of NTD3 through SwissADME indicated that most of the predicted parameters including Lipinski rule were within acceptable limits. While these findings are promising, further research is necessary to elucidate the precise relationships between the chemical structures and their activity, as well as to understand the mechanisms underlying their pharmacological effects. This study lays the foundation for the development of novel anti-inflammatory therapeutics, potentially offering improved efficacy and safety profiles.

Oral feed-based administration of phage cocktail protects rohu fish (Labeo rohita) against Aeromonas hydrophila infection.

Aeromonas hydrophila is one of the major freshwater fish pathogens. In the current study, a cocktail of D6 and CF7 phages was given orally to Labeo rohita to assess phage survival in fish organs as well as to determine the therapeutic efficacy of phage treatment against fish mortality caused by A. hydrophila. In the phage-coated feed, prepared by simple spraying method, phage counts were quite stable for up to 2 months with a decline of ≤ 0.23 log10 and ≤ 1.66 log10 PFU/g feed during 4 oC and room temperature storage. Throughout the experimental period of 7 days, both phages could be detected in the gut of fish fed with phage-coated feed. Besides, both CF7 and D6 phages were also detected in fish kidneys indicating the ability of both the phage to cross the intestinal barrier. During challenge studies with LD50 dose of A. hydrophila, phage cocktail doses of 1 × 106 - 1 × 108 PFU/g feed prevented the mortality in L. rohita with relative percentage survival (RPS) of 8.7-65.2. When challenged with LD90 dose of A. hydrophila, an RPS value of 28.6 was obtained at a phage cocktail dose of 1 × 108 PFU/g feed. The RPS data showed that orally-fed phage cocktail protected the fish against the mortality caused by A. hydrophila in a dose-dependent manner. Simple practical approaches for phage cocktail development, medicated feed preparation and oral administration along with phage survival and protection data make the current study useful for farmer-level application.

De Novo Purine Metabolism is a Metabolic Vulnerability of Cancers with Low p16 Expression.

p16 is a tumor suppressor encoded by the CDKN2A gene whose expression is lost in approximately 50% of all human cancers. In its canonical role, p16 inhibits the G1-S-phase cell cycle progression through suppression of cyclin-dependent kinases. Interestingly, p16 also has roles in metabolic reprogramming, and we previously published that loss of p16 promotes nucleotide synthesis via the pentose phosphate pathway. However, the broader impact of p16/CDKN2A loss on other nucleotide metabolic pathways and potential therapeutic targets remains unexplored. Using CRISPR knockout libraries in isogenic human and mouse melanoma cell lines, we determined several nucleotide metabolism genes essential for the survival of cells with loss of p16/CDKN2A. Consistently, many of these genes are upregulated in melanoma cells with p16 knockdown or endogenously low CDKN2A expression. We determined that cells with low p16/CDKN2A expression are sensitive to multiple inhibitors of de novo purine synthesis, including antifolates. Finally, tumors with p16 knockdown were more sensitive to the antifolate methotrexate in vivo than control tumors. Together, our data provide evidence to reevaluate the utility of these drugs in patients with p16/CDKN2Alow tumors as loss of p16/CDKN2A may provide a therapeutic window for these agents. SIGNIFICANCE: Antimetabolites were the first chemotherapies, yet many have failed in the clinic due to toxicity and poor patient selection. Our data suggest that p16 loss provides a therapeutic window to kill cancer cells with widely-used antifolates with relatively little toxicity.