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Global healthcare systems have faced unprecedented strain due to the COVID-19 pandemic, with a profound impact on individuals with non-communicable diseases (NCDs), a scenario particularly pronounced in low-income countries like Nepal. This study aimed to understand the experiences of and challenges faced by patients with NCDs in Nepal during the pandemic, focusing on healthcare service availability and identifying factors affecting healthcare use, with the goal of being prepared for future emergencies. This study utilized a telephonic survey of 102 patients with NCDs and 10 qualitative interviews with healthcare providers in the Kavrepalanchok and Nuwakot districts of Nepal. We used mixed methods, with both qualitative and quantitative approaches. Specifically, multiple correspondence analysis, hierarchical cluster analysis, and classification tree analysis were used as exploratory methods. The study revealed that while 69.6% of the participants reported no difficulty in obtaining medication, other questions revealed that 58.8% experienced challenges in accessing routine medical care. Major barriers, such as fear of infection, unavailability of medicine in rural areas, and lack of transportation, were found through the qualitative interviews. Meanwhile, participants identified innovative strategies, such as telemedicine and community-based awareness programs, as potential facilitators for addressing barriers that arise during pandemic situations such as COVID-19. The COVID-19 pandemic exacerbated challenges in accessing healthcare services for patients with NCDs in Nepal. Our findings suggest the need to design and implement telemedicine services for patients with NCDs, as well as community-based programs that aim to improve health literacy, encourage healthy behavior, prevent development of NCDs, and ensure continuity of care during such crises, especially in countries with limited resources., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Iwashita et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Efficient removal of 4-aminophenylarsonic acid from contaminated water sources is essential to mitigate arsenic pollution. We proposed a competent technique to achieve 4-aminophenylarsonic acid removal via adsorption on enhanced α-FeOOH using various concentrations of Mn(VII). The elimination rate of 4-aminophenylarsonic acid applying FeOOH with Mn(VII) was dependent on acidic conditions. More than 99.9% of 4-aminophenylarsonic acid was eliminated in a 6-min reaction time under acidic conditions. The reaction of 4-aminophenylarsonic acid was fast at 4.0 and 5.0 pH, with its complete oxidation into arsenate and the liberation of manganese Mn(II) in the initial stage of the reaction. Similarly, the reaction rate constant (k obs ) decreased from 0.7048 ± 0.02 to 0.00155 ± 0.00007 as the pH increased from 4.0 to 9.0. Oxidation capacity was considerably enhanced via the removal of electrons from 4-aminophenylarsonic acid to Mn(VII) after the creation of its radical intermediate and further change in Mn(III) to Mn(II) in the solution. The results showed that Mn(VII) played a crucial role in 4-aminophenylarsonic acid degradation at a low pH (e.g., 4.0), and the oxidation process proceeded in different manners, namely, electron transfer, hydroxylation, and ring-opening. These results illustrated that Mn(VII) is an effective, economic purification process to mitigate 4-aminophenylarsonic acid generated from poultry waste., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The creation of large amounts of excess sludge and residual nitrogen are critical issues in wastewater biotreatment. This study introduced Fe(II) into an oligotrophic anaerobic reactor (OAR Fe ) that was implemented to modify an anoxic-oxic process to motivate in-situ sludge reduction and enhance denitrification under an effective electron shuttle among organic matter, nitrogen, and Fe. The addition of 15 mg L -1 Fe(II) resulted in a sludge reduction efficiency reached 32.0% with a decreased effluent nitrate concentration of 33.3%. This was mostly attributed to the electron transfer from Fe(II) to organic matters and nitrogen species in OAR Fe . The participation of Fe(II) led to the upregulation of Geothrix and Terrimonas, which caused active organic matter hydrolysis and cell lysis to stimulate the release of extracellular polymeric substances (EPS) and substance transfer between each layer of EPS. The higher utilization of released bioavailable dissolved organic matter improved endogenous denitrification, which can be combined with iron autotrophic denitrification to realize multiple electron donor-based nitrogen removal pathways, resulting in an increased nitrate removal rate of 58.2% in the absence of external carbon sources. These functional bacteria associated with the transformation of nitrogen and carbon and cycling between ferrous and ferric ions were enriched in OAR Fe , which contributed to efficient electron transport occurred both inside and outside the cell and increased 2,3,5-triphenyltetrazolium chloride electronic transport system activity by 46.9%. This contributed to the potential operational costs of chemical addition and sludge disposal of Fe-AO being 1.9 times lower than those of conventional A 2 O processes. These results imply that the addition of ferrous ions to an oligotrophic anaerobic zone for wastewater treatment has the potential for low-cost pollution control., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Violence against women (VAW), particularly intimate partner violence (IPV) or domestic violence, is a major public health issue, garnering more attention globally post-coronavirus disease 2019 (COVID-19) lockdown. Health providers often represent the first point of contact for IPV victims. Thus, health systems and health providers must be equipped to address survivors' physical, sexual and mental health care needs. However, there is a notable lack of evidence regarding such readiness in Nepal. This study, utilizing a concurrent triangulation design, evaluated the readiness of public health facilities in Nepal's Madhesh Province in managing VAW, focusing on providers' motivation to offer psychosocial counselling to survivors. A cross-sectional study was conducted across 11 hospitals and 17 primary health care centres, where 46 health care providers were interviewed in February-April 2022. The study employed the World Health Organization's tools for policy readiness and the Physician Readiness to Manage IPV Survey for data collection. Quantitative and qualitative data were collected via face-to-face interviews and analysed using descriptive and content analysis, respectively. Only around 28% of health facilities had trained their staff in the management of VAW. Two out of 11 hospitals had a psychiatrist, and a psychosocial counsellor was available in four hospitals and two out of 17 primary health care centres. Two-thirds of all health facilities had designated rooms for physical examinations, but only a minority had separate rooms for counselling. Though a few health facilities had guidelines for violence management, the implementation of these guidelines and the referral networks were notably weak. Hospitals with one-stop crisis management centres demonstrated readiness in VAW management. Health providers acknowledged the burden of IPV or domestic violence and expressed motivation to deliver psychosocial counselling, but many had limited knowledge. This barrier can only be resolved through appropriate training and investment in violence management skills at all tiers of the health system., (© The Author(s) 2024. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.)

Background: Transurethral resection of bladder tumor (TURBT) is associated with perioperative morbidity of 5% to 10%, which can lead to unplanned readmissions. In this study, we aimed to identify the factors that lead to an increased risk of unplanned readmissions within 30 days of primary TURBT., Materials and Methods: A retrospective study was conducted to identify patients who underwent primary TURBT at our institute from 2011 to 2019. Clinical and demographic factors, history of smoking, antiplatelet drugs intake, comorbidities, tumor size (<3 or >3 cm), multifocality, and histopathological type were abstracted. Patients who were readmitted were identified, and reasons for admission were recorded., Results: A total of 435 patients were identified. The median age of the patients was 66 years. From 378 male patients (86.9%), 110 (25.3%) and 37 (8.5%) had a history of smoking and antiplatelet agents intake, respectively. In the cohort, 166 patients (38.2%) were diabetic, 239 (54.9%) were hypertensive, 72 (16.6%) had chronic obstructive pulmonary disease, and 78 (7.9%) had hypothyroidism. A total of 206 patients (47.4%) had a tumor >3 cm; multifocality was seen in 140 (32.2%) patients, whereas muscle invasive tumors were present in 161 patients (37%). A total of 22 patients (5.06%) had readmissions within 30 days, with hematuria being the most common etiology. On univariate and multivariate analyses, a history of smoking ( p = 0.006 and p = 0.008, respectively) or antiplatelet agents intake ( p < 0.001 and p < 0.001, respectively) was significantly associated with increased unplanned readmission., Conclusions: Our study revealed smoking and antiplatelet agents intake as factors leading to an increased risk of unplanned readmissions., Competing Interests: No conflict of interest has been declared by the authors., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc.)

Background: Type 2 diabetes mellitus (T2DM) has increased globally; with a disproportionate burden in South and Southeast Asian countries, including Nepal. There is an urgent need for clinically and cost-effective culturally adapted T2DM management programs. In this study, we aim to assess the effectiveness of community based culturally appropriate lifestyle intervention in improving the management and care of people with T2DM., Methods: We will conduct a cluster randomized control trial to evaluate the effectiveness of community based culturally appropriate lifestyle intervention in improving T2DM outcomes. The trial will be conducted in 30 randomly selected healthcare facilities from two purposively selected districts (Kavrepalanchowk and Nuwakot districts) of Bagmati province, Nepal. The selected healthcare facilities are being randomized into 15 interventions (n = 15) and usual care (n = 15) groups. Those in the intervention will receive group-based 12 an hour-long fortnightly session delivered over 6 months period. The intervention package includes 12 planned modules related to diabetes care, ongoing support, supervision and monitoring, follow-up from the trained community health workers, and educational materials on diabetes self-management. The participants in the usual care groups will receive pictorial brochure on diabetes management and they will continue receiving the usual care available from the local health facilities. The primary outcome is HbA1c level, and the secondary outcomes include quality of life, health care utilization, and practice of self-care behaviour, depression, oral health quality of life, and economic assessment of the intervention. Two points measurements will be collected by the trained research assistants at baseline and at the end of the intervention., Discussion: This study will provide tested approaches for culturally adapting T2DM interventions in the Nepalese context. The findings will also have practice and policy implications for T2DM prevention and management in Nepal., Trial Registration: Australia and New Zealand Clinical Trial Registry (ACTRN12621000531819). Registered on May 6, 2021., (© 2023. The Author(s).)

Background: After COVID-19 was declared a Public Health Emergency of International Concern by WHO, several non-pharmaceutical interventions were adopted for containing the virus. Success to which largely depend upon citizens' compliance to these measures. There is growing body of evidence linking social support with health promoting behaviour. Hence, this research aimed to study the effects on compliance with stay-at-home order in relation to their perceived social support., Methods: A web-based cross-sectional study was conducted among adult participants aged 18 years and above residing in Bagmati Province, Nepal. A convenient non-probability sampling method was adopted to select the required number of samples. The questionnaire was developed through an extensive review of literature, and consultations with the research advisor, subject experts, as well as peers and converted to online survey form using Google Forms. Perceived social support was measured using the Multidimensional Scale of Perceived Social Support (MSPSS) scale whereas compliance was assessed using a single screening question. Statistical analysis was performed using SPSS version 20 involving both the descriptive and inferential statistics., Results: Two fifth (40.2%) of the participants reported poor compliance with stay-at-home order which was found higher among participants who were not vaccinated against COVID-19 compared to those vaccinated (p value < 0.05). A significant difference was observed between sex and perceived support (p value < 0.05) with higher proportion (80.8%) of female participants reporting perceived support from family, friends, and significant others in comparison to male participants., Conclusion: Overall, the results of this study suggest that the perceived support from family is higher compared to others. Further evidence might be helpful to understand contextual factors on compliance with public health measures. Tailoring behaviour change messages as per the community needs would help the response in such emergencies. The findings from this study might be useful as one of the evidence base for formulating plans and policy during emergencies of similar nature., (© 2023. The Author(s).)

Given the scarcity of data on diabetes prevalence and associated risk factors among women in rural Nepal, we aimed to examine this, using glycated hemoglobin (HbA1c) as a diagnostic tool. A cross-sectional survey addressing reproductive health and non-communicable diseases was conducted in 2012-2013 among non-pregnant, married women in Bolde, a rural district of Nepal. HbA1c ≥ 6.5% (48 mmol/mol) was used as diagnostic criterion for diabetes, a cut-off of 7.0% (53 mmol/mol) was used to increase the specificity. HbA1c was measured in 757 women (17-86 years). The prevalence of diabetes and prediabetes was 13.5% and 38.5%, respectively. When using 7.0% as a cut-off, the prevalence of diabetes was 5.8%. Aging, intake of instant noodles and milk and vegetarian food (ns) were associated with increased risk for diabetes. Waist circumference was higher among women with diabetes, although not significant. The women were uneducated (87.6%), and only 12% had heard about diabetes. In conclusion, we observed a higher prevalence of diabetes and prediabetes than anticipated among rural, Nepalese women. The increased risk was mainly attributed to dietary factors. In contrast to most previous studies in Nepal, we used HbA1c as diagnostic criterion.

If we can use toxic aromatic compounds as supplementary carbon source, the simultaneous removal of nitrate (NO 3 - ) and aromatic compounds may be achieved at much lower chemical costs. This study uses the expanded granular sludge bed (EGSB) reactors to investigate the hypersaline (> 3%) denitrification performance, the removal of aromatic compounds, i.e., aniline, phenol, and their mixture, and the mechanisms involved in. The four reactors exhibit high removal efficiency of NO 3 - (> 92.8%) and aromatic compounds (> 73.9%) at 0-1200 mg/L of aromatic compounds. The formation of toxic intermediates such as catechol and azo dyes is revealed by gas chromatography mass spectrometry (GC-MS) with and without N,O-Bis(trimethylsilyl) trifluoroacetamide (BSTFA) derivation, and their toxic effects lead to the lower cell survival ratios after exposing to phenol (64.2% ∼ 68.9%) than to aniline and mixture (72.7% ∼ 78.0%). The stable performance is associated with the more secretion of extracellular polymeric substances (EPS) and the adsorption of pollutants on EPS, and this was indicated from the higher fluorescence intensity in three-dimensional excitation-emission matrix (3D-EEM). Moreover, the Halomonas and Azoarcus show high abundance and play important roles in the removal of both NO 3 - and aromatic compounds. Besides, quantitative real time PCR (RT-qPCR) results demonstrate the key role of highly abundant nosZ and nirS genes in denitrification. The toxic organics in industrial wastewaters are potentially feasible carbon sources for denitrification even under high-salinity stress., (Copyright © 2022. Published by Elsevier Ltd.)

Hypovitaminosis D is prevalent worldwide, and especially in South-Asia. According to the Institute of Medicine (IOM), 25(OH)D levels below 30 nmol/L are defined as vitamin D deficiency (VDD) and levels between 30−50 nmol/L as insufficiency (VDI). Besides its role in calcium homeostasis, it has been postulated that vitamin D is involved in metabolic syndrome. Given the scarcity of data on vitamin D status in Nepal, we aimed to examine the prevalence of VDD and VDI, as well as the determinants and association with metabolic parameters (lipids, HbA1c), in a cohort of women in rural Nepal. Altogether, 733 women 48.5 ± 11.7 years of age were included. VDD and VDI were observed in 6.3 and 42.4% of the participants, respectively, and the prevalence increased by age. Women reporting intake of milk and eggs > 2 times weekly had higher 25(OH)D levels than those reporting intake < 2 times weekly. Women with vitamin D levels < 50 nmol/L displayed higher levels of cholesterol, LDL-cholesterol, triglycerides, and HbA1c. Additionally, a regression analysis showed a significant association between hypovitaminosis D, dyslipidemia, and HbA1c elevation. In conclusion, VDI was prevalent and increased with age. Milk and egg intake > 2 times weekly seemed to decrease the risk of VDI. Moreover, hypovitaminosis D was associated with an adverse metabolic profile.

Perivascular epithelioid cell tumors (PEComas) are a group of tumours of mesenchymal origin having a characteristic pathological presence of the epitheloid cell around blood vessels. They are uncommon tumours and hence their exact etiology and pathogenesis remain unclear. They can occur at any part of the body but the common sites of involvement are the gastrointestinal system and the genitourinary system. The isolated involvement of the intestinal mesentery is very rare, with only a few cases reported in the literature till date. The involvement of lymph nodes by these tumours is exceptionally rare. We report a hitherto undescribed case of mesenteric PEComa in a young female who developed para-aortic nodal metastasis., (© 2022. Japanese Society of Gastroenterology.)

Background: Nepal, in recent years, is witnessing an increasing problem of type 2 diabetes that has resulted significant premature deaths and disability. Prevention and management of non-communicable diseases (NCDs) including diabetes have been prioritized in the national policies and guidelines of the Nepal Government. However, research looking at the overview of the implementation of the existing policies and guidelines for diabetes prevention and control is scarce. Hence, this study reviewed diabetes related existing policies and its implementation process at the primary health care level in Nepal., Methods: This study involved two phases: Phase I: situation analyses through review of documents and Phase II: qualitative exploratory study. In phase I, four databases (Medline, Web of Science, Embase and PubMed) were systematically searched using key search terms related to diabetes care and policies between January 2000 and June 2021. Also, relevant gray literature was reviewed to understand the trajectory of policy development and its translation with regards to diabetes prevention and management at primary health care level in Nepal. Following the phase I, we conducted in-depth interviews (IDI) and key informant interviews (KII) with health care providers, policy makers, and managers (IDI = 13, and KII = 7) at peripheral and central levels in Kavrepalanchowk and Nuwakot districts of Nepal. The in-depth interviews were audio recorded, transcribed, and coded. The triangulation of data from document review and interviews was done and presented in themes., Results: Four key themes were identified through triangulating findings from the document review and interviews including (i) limited implementation of policies into practices; (ii) lack of coordination among the different levels of service providers; (iii) lack of trained human resources for health and inadequate quality services at the primary health care level, and (iv) inadequate access and utilization of diabetes care services at primary health care level. Specifically, this study identified some key pertinent challenges to the implementation of policies and programs including inadequate resources, limited engagement of stakeholders in service design and delivery, lack of trained health care providers, lack of financial resources to strengthen peripheral health services, fragmented health governance, and weak reporting and monitoring systems., Conclusion: This study revealed that the policies, plans, and strategies for prevention and management of NCDs in Nepal recognized the importance of diabetes prevention and control. However, a major gap remains with adequate and lack of clarity in terms of implementation of available policies, plans, strategies, and programs to address the problem of diabetes. We suggest the need for multisectoral approach (engaging both health and non-health sectors) at central as well as peripheral levels to strengthen the policies implementation process, building capacity of health care providers, ensuring adequate financial and non-financial resources, and improving quality of services at primary health care levels., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Shrestha, Yadav, Shrestha, Paudel, Makaju, Poudel, Iwashita, Harada, Shrestha, Karmacharya, Koju, Sugishita and Rawal.)

Background: Hypertension and headache disorders are major contributors to public ill health, linked by a long-standing but questionable belief that hypertension is a conspicuous cause of headache. In Nepal, where hypertension is common and often untreated, we assessed the substance of this belief, hypothesising that, should hypertension be a significant cause of headache, a clear positive association between these disorders would exist., Methods: In a cross-sectional, nationwide study, trained health workers conducted face-to-face structured interviews, during unannounced home visits, with a representative sample of the Nepalese adult population (18-65 years). They applied standard diagnostic criteria for headache disorders and measured blood pressure digitally. Hypertension was defined as systolic pressure ≥140 and/or diastolic ≥90 mm Hg., Results: Of 2,100 participants (59.0% female, mean age 36.4 ± 12.8 years), 317 (15.1%) had hypertension (41.0% female) and 1,794 (85.4%) had headache (61.6% female; 728 migraine, 863 tension-type headache, 161 headache on ≥15 days/month [mutually exclusive diagnoses]; 42 unclassified headaches).All headache collectively was less prevalent among hypertension cases (78.9%) than non-cases (86.6%; p = 0.001). A negative association between hypertension and all headache was demonstrated in bivariate analysis (odds ratio: 0.6 [95% Confidence interval: 0.4-0.8]; p < 0.001), but did not maintain significance in multivariate regression analysis (adjusted odds ratio: 0.8 [95% Confidence interval: 0.5-1.1]; p = 0.09). The findings were reflected, without significance, in each headache type., Conclusions: If any association exists between hypertension and headache disorders, it is negative. From the public-health perspective, headache disorders and hypertension are unrelated entities: they need distinct policies and programs for prevention, control and management.

Background: Cardiovascular diseases (CVDs) are the leading cause of deaths and disability in Nepal. Health systems can improve CVD health outcomes even in resource-limited settings by directing efforts to meet critical system gaps. This study aimed to identify Nepal's health systems gaps to prevent and manage CVDs., Methods: We formed a task force composed of the government and non-government representatives and assessed health system performance across six building blocks: governance, service delivery, human resources, medical products, information system, and financing in terms of equity, access, coverage, efficiency, quality, safety and sustainability. We reviewed 125 national health policies, plans, strategies, guidelines, reports and websites and conducted 52 key informant interviews. We grouped notes from desk review and transcripts' codes into equity, access, coverage, efficiency, quality, safety and sustainability of the health system., Results: National health insurance covers less than 10% of the population; and more than 50% of the health spending is out of pocket. The efficiency of CVDs prevention and management programs in Nepal is affected by the shortage of human resources, weak monitoring and supervision, and inadequate engagement of stakeholders. There are policies and strategies in place to ensure quality of care, however their implementation and supervision is weak. The total budget on health has been increasing over the past five years. However, the funding on CVDs is negligible., Conclusion: Governments at the federal, provincial and local levels should prioritize CVDs care and partner with non-government organizations to improve preventive and curative CVDs services.

Laparoscopic nephrectomy is a commonly performed procedure. As with any surgical procedure, this too has a significant learning curve. The management of renal hilum is the most critical part of this surgery. It requires a meticulous intra-hilar dissection to identify the renal artery and vein. The kidneys are extremely vascular structures and any injury to these vessels during dissection can result in life-threatening bleeding. Hence, it is obvious that beginners most often face difficulty and apprehension at this step of the laparoscopic nephrectomy. We describe a simple technique of laparoscopic nephrectomy which includes the creation of two windows, one at the lower pole and the second at the upper pole, isolation of the hilum, and en bloc stapling of the renal hilar vessels. This method safeguards against collateral damage to the surrounding structures. It also avoids the need for intra-hilar dissection, hence decreasing the chances of vascular injuries., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Jindal et al.)

Objective: To explore the perception of obesity and overweight among Nepalese adults living in a suburban community., Design: A qualitative study composed of focus group discussion (FGD) and in-depth interview (IDI)., Setting: Community and healthcare facilities in Dhulikhel, Nepal., Participants: Four FGDs were conducted with community members (n=22) and four IDIs were conducted with healthcare providers (HCPs)., Results: Obesity is a rising problem in this suburban community. Participants had inadequate knowledge regarding the consequences of obesity, and they perceived overweight as normal, healthy and attractive. The participants above 40 years of age did not perceive themselves to be overweight or obese. Despite participants' awareness of the importance of diet control and exercise to prevent obesity, these were not translated into practice., Conclusions: This study provided insight into perceptions of obesity in a suburban Dhulikhel community through both community members' and HCPs' perspective. Misconceptions and inadequate knowledge of obesity among people in this community indicate the need for health education and intervention programme to increase health awareness and preventive practices., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

While chronic lung disease causes substantial global morbidity and mortality, global estimates have primarily been based on broad assumptions. Specific country data from low-income countries such as Nepal are limited. This review assessed primary evidence on chronic respiratory disease burden among adults in Nepal. A systematic search was performed in June 2019 (updated May 2020) for studies through nine databases. High levels of heterogeneity deemed a narrative synthesis appropriate. Among 27 eligible studies identified, most were low-moderate quality with cross-sectional and retrospective study design. Chronic lung diseases identified were chronic obstructive pulmonary disease (COPD), asthma, bronchiectasis and restrictive lung diseases. Studies were categorised as: (i) community-based, (ii) hospital-based and (iii) comorbidity-related and disease burden. Reported disease prevalence varied widely (COPD, 1.67-14.3%; asthma, 4.2-8.9%). The prevalence of airflow obstruction was higher among rural dwellers (15.8%) and those exposed to household air pollution from domestic biomass burning as opposed to liquid petroleum gas users (Odds Ratio: 2.06). Several comorbidities, including hypertension and diabetes mellitus added to the disease burden. The review shows limited literature on lung disease burden in Nepal. Publications varied in terms of overall quality. Good quality research studies with prospective cohorts related to respiratory conditions are required.

Biological denitrification is an environmentally sound pathway for the elimination of nitrogen pollution in wastewater treatment. Extreme environmental conditions, such as the co-existence of toxic organic pollutants, can affect biological denitrification. However, the potential underlying mechanism remains largely unexplored. Herein, the effect of a model pollutant, hydroxyethane-(1,1-bisphosphonic acid) (HEDP), a widely applied and consumed bisphosphonate, on microbial denitrification was investigated by exploring the metabolic and transcriptional responses of an isolated denitrifier, Pannonibacter sp. strain DN. Results showed that nitrate removal efficiency decreased from 85% to 50% with an increase in HEDP concentration from 0 to 3.5 mM, leading to nitrite accumulation of 204 mg L -1 in 3.5 mM HEDP. This result was due to the lower bacterial population count and reduction in the live cell percentage. Further investigation revealed that HEDP caused a decrease in membrane potential from 0.080 ± 0.005 to 0.020 ± 0.002 with the increase in HEDP from 0 to 3.5 mM. This hindered electron transfer, which is required for nitrate transformation into nitrogen gas. Moreover, transcriptional profiling indicated that HEDP enhanced the genes involved in ROS (O 2 - ) scavenging, thus protecting cells against oxidative stress damage. However, the suppression of genes responsible for the production of NADH/FADH 2 in tricarboxylic acid cycle (TCA), NADH catalyzation (NADH dehydrogenase) in (electron transport chain) ETC system and denitrifying genes, especially nor and nir, in response to 2.5 mM HEDP were identified as the key factor inhibiting transfer of electron from TCA cycle to denitrifying enzymes through ETC system., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)