Displaying publications 1 - 20 of 63 in total

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  1. Yap KP, Gan HM, Teh CS, Baddam R, Chai LC, Kumar N, et al.
    J Bacteriol, 2012 Nov;194(21):5970-1.
    PMID: 23045488 DOI: 10.1128/JB.01416-12
    Salmonella enterica serovar Typhi is a human pathogen that causes typhoid fever predominantly in developing countries. In this article, we describe the whole genome sequence of the S. Typhi strain CR0044 isolated from a typhoid fever carrier in Kelantan, Malaysia. These data will further enhance the understanding of its host persistence and adaptive mechanism.
  2. Yap KP, Teh CS, Baddam R, Chai LC, Kumar N, Avasthi TS, et al.
    J Bacteriol, 2012 Sep;194(18):5124-5.
    PMID: 22933756 DOI: 10.1128/JB.01062-12
    Salmonella enterica serovar Typhi is the causative agent of typhoid fever, which causes nearly 21.7 million illnesses and 217,000 deaths globally. Herein, we describe the whole-genome sequence of the Salmonella Typhi strain ST0208, isolated from a sporadic case of typhoid fever in Kuala Lumpur, Malaysia. The whole-genome sequence and comparative genomics allow an in-depth understanding of the genetic diversity, and its link to pathogenicity and evolutionary dynamics, of this highly clonal pathogen that is endemic to Malaysia.
  3. Wadhwa R, Aggarwal T, Malyla V, Kumar N, Gupta G, Chellappan DK, et al.
    J Cell Physiol, 2019 08;234(10):16703-16723.
    PMID: 30912142 DOI: 10.1002/jcp.28482
    Chronic obstructive pulmonary disease accounts as the leading cause of mortality worldwide prominently affected by genetic and environmental factors. The disease is characterized by persistent coughing, breathlessness airways inflammation followed by a decrease in forced expiratory volume1 and exacerbations, which affect the quality of life. Determination of genetic, epigenetic, and oxidant biomarkers to evaluate the progression of disease has proved complicated and challenging. Approaches including exome sequencing, genome-wide association studies, linkage studies, and inheritance and segregation studies played a crucial role in the identification of genes, their pathways and variation in genes. This review highlights multiple approaches for biomarker and gene identification, which can be used for differential diagnosis along with the genome editing tools to study genes associated with the development of disease and models their function. Further, we have discussed the approaches to rectify the abnormal gene functioning of respiratory tissues and various novel gene editing techniques like Zinc finger nucleases (ZFN), transcription activator-like effector nucleases (TALEN), and clustered regulatory interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9).
  4. Wadhwa R, Pandey P, Gupta G, Aggarwal T, Kumar N, Mehta M, et al.
    Curr Top Med Chem, 2019;19(28):2593-2609.
    PMID: 31746290 DOI: 10.2174/1568026619666191026105308
    BACKGROUND: Candida species are the important etiologic agents for candidiasis, the most prevalent cause of opportunistic fungal infections. Candida invasion results in mucosal to systemic infections through immune dysfunction and helps in further invasion and proliferation at several sites in the host. The host defence system utilizes a wide array of the cells, proteins and chemical signals that are distributed in blood and tissues which further constitute the innate and adaptive immune system. The lack of antifungal agents and their limited therapeutic effects have led to high mortality and morbidity related to such infections.

    METHODS: The necessary information collated on this review has been gathered from various literature published from 1995 to 2019.

    RESULTS: This article sheds light on novel drug delivery approaches to target the immunological axis for several Candida species (C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, C. krusei, C. rugose, C. hemulonii, etc.).

    CONCLUSION: It is clear that the novel drug delivery approaches include vaccines, adoptive transfer of primed immune cells, recombinant cytokines, therapeutic antibodies, and nanoparticles, which have immunomodulatory effects. Such advancements in targeting various underpinning mechanisms using the concept of novel drug delivery will provide a new dimension to the fungal infection clinic particularly due to Candida species with improved patient compliance and lesser side effects. This advancement in knowledge can also be extended to target various other similar microbial species and infections.

  5. Veerasamy C, Sambasivan M, Kumar N
    PLoS One, 2013;8(10):e77698.
    PMID: 24194894 DOI: 10.1371/journal.pone.0077698
    The purpose of this paper is to analyze two important outcomes of individual skills-based volunteerism (ISB-V) among healthcare volunteers in Malaysia. The outcomes are: job performance and life satisfaction. This study has empirically tested the impact of individual dimensions of ISB-V along with their inter-relationships in explaining the life satisfaction and job performance. Besides, the effects of employer encouragement to the volunteers, demographic characteristics of volunteers, and self-esteem of volunteers on job performance and life satisfaction have been studied. The data were collected through a questionnaire distributed to 1000 volunteers of St. John Ambulance in Malaysia. Three hundred and sixty six volunteers responded by giving their feedback. The model was tested using Structural Equation Modeling (SEM). The main results of this study are: (1) Volunteer duration and nature of contact affects life satisfaction, (2) volunteer frequency has impact on volunteer duration, (3) self-esteem of volunteers has significant relationships with volunteer frequency, job performance and life satisfaction, (4) job performance of volunteers affect their life satisfaction and (5) current employment level has significant relationships with duration of volunteering, self esteem, employer encouragement and job performance of volunteers. The model in this study has been able to explain 39% of the variance in life satisfaction and 45% of the variance in job performance. The current study adds significantly to the body of knowledge on healthcare volunteerism.
  6. Usman MB, Ojha S, Jha SK, Chellappan DK, Gupta G, Singh SK, et al.
    J Integr Neurosci, 2022 Jan 28;21(1):41.
    PMID: 35164477 DOI: 10.31083/j.jin2101041
    Computational approach to study of neuronal impairment is rapidly evolving, as experiments and intuition alone could not explain the complexity of brain system. The increase in an overwhelming amount of new data from both theory and computational modeling necessitate the development of databases and tools for analysis, visualization, and interpretation of neuroscience data. To ensure the sustainability of this development, consistent update and training of young professionals are imperative. For this purpose, relevant articles, chapters, and modules are essential to keep abreast of developments. Therefore, this article seeks to outline the biological databases and analytical tools along with their applications. It's envisaged that knowledge along this line would be a "training recipe" for young talents and guide for professionals and researchers in neuroscience.
  7. Toller Erausquin J, Tan RKJ, Uhlich M, Francis JM, Kumar N, Campbell L, et al.
    Clin Infect Dis, 2022 Aug 24;75(1):e991-e999.
    PMID: 35136960 DOI: 10.1093/cid/ciac102
    BACKGROUND: There is limited evidence to date about changes to sexual and reproductive health (SRH) during the initial wave of coronavirus disease 2019 (COVID-19). To address this gap, our team organized a multicountry, cross-sectional online survey as part of a global consortium.

    METHODS: Consortium research teams conducted online surveys in 30 countries. Sampling methods included convenience, online panels, and population-representative. Primary outcomes included sexual behaviors, partner violence, and SRH service use, and we compared 3 months prior to and during policy measures to mitigate COVID-19. We conducted meta-analyses for primary outcomes and graded the certainty of the evidence.

    RESULTS: Among 4546 respondents with casual partners, condom use stayed the same for 3374 (74.4%), and 640 (14.1%) reported a decline. Fewer respondents reported physical or sexual partner violence during COVID-19 measures (1063 of 15 144, 7.0%) compared to before COVID-19 measures (1469 of 15 887, 9.3%). COVID-19 measures impeded access to condoms (933 of 10 790, 8.7%), contraceptives (610 of 8175, 7.5%), and human immunodeficiency virus/sexually transmitted infection (HIV/STI) testing (750 of 1965, 30.7%). Pooled estimates from meta-analysis indicate that during COVID-19 measures, 32.3% (95% confidence interval [CI], 23.9%-42.1%) of people needing HIV/STI testing had hindered access, 4.4% (95% CI, 3.4%-5.4%) experienced partner violence, and 5.8% (95% CI, 5.4%-8.2%) decreased casual partner condom use (moderate certainty of evidence for each outcome). Meta-analysis findings were robust in sensitivity analyses that examined country income level, sample size, and sampling strategy.

    CONCLUSIONS: Open science methods are feasible to organize research studies as part of emergency responses. The initial COVID-19 wave impacted SRH behaviors and access to services across diverse global settings.

  8. Tiwari A, Gopalan Kutty N, Kumar N, Chaudhary A, Vasanth Raj P, Shenoy R, et al.
    Cytotechnology, 2016 Dec;68(6):2553-2565.
    PMID: 27282155 DOI: 10.1007/s10616-016-9979-9
    The oxadiazole moiety is known for its anticancer activity through its antiangiogenic and mitostatic potential. Taking this as a cue, the present study was designed to investigate the anti-cancer potential of selected oxadiazole derivatives. Twelve 1,3,4-oxadiazole derivatives (AMK OX-1 to AMK OX-12) were synthesized and were tested for IC50values through brine shrimp lethality assay and MTT assay on HeLa and A549 cell lines. Four compounds, AMK OX-8, 9, 11 and 12 showed potential cytotoxicity activity with low IC50value. These compounds produced considerable cytotoxic effect on Hep-2 and A549 cancer cell lines. However, they were found to be comparatively safer to normal cell lines, viz., V-79 cell lines than to the tested cancer cell lines, such as HeLa, A 549, and Hep2 cell lines. The mechanism of cytotoxicity was evaluated through nuclear staining and DNA ladder assay. Although DNA ladder assay showed DNA fragmentation (apoptotic phenomenon) in Hep-2 cells treated with only AMK OX-12, the staining procedures using acridine orange, ethidium bromide and propidium iodide showed apoptotic bodies in cells treated with AMK OX-8, 9 and 12 also. In JCI staining on isolated mitochondria of Hep2 cells, AMK OX-8, 9-11 and 12 displayed increasing fluorescence intensity with time which confirmed involvement of mitochondrial pathway and intrinsic pathway of apoptosis. All four compounds were found to be safe in acute oral toxicity study in Swiss albino mice. These derivatives were effective in reducing tumor size and weight in the in vivo DLA-induced solid tumor model. They were found to be significantly effective in reducing tumor volume and tumor weight.
  9. Tiruvayipati S, Bhassu S, Kumar N, Baddam R, Shaik S, Gurindapalli AK, et al.
    Gut Pathog, 2013 Dec 11;5(1):37.
    PMID: 24330647 DOI: 10.1186/1757-4749-5-37
    Vibrio parahaemolyticus, an important human pathogen, is associated with gastroenteritis and transmitted through partially cooked seafood. It has become a major concern in the production and trade of marine food products. The prevalence of potentially virulent and pathogenic V. parahaemolyticus in raw seafood is of public health significance. Here we describe the genome sequence of a V. parahaemolyticus isolate of crustacean origin which was cultured from prawns in 2008 in Selangor, Malaysia (isolate PCV08-7). The next generation sequencing and analysis revealed that the genome of isolate PCV08-7 has closest similarity to that of V. parahaemolyticus RIMD2210633. However, there are certain unique features of the PCV08-7 genome such as the absence of TDH-related hemolysin (TRH), and the presence of HU-alpha insertion. The genome of isolate PCV08-7 encodes a thermostable direct hemolysin (TDH), an important virulence factor that classifies PCV08-7 isolate to be a serovariant of O3:K6 strain. Apart from these, we observed that there is certain pattern of genetic rearrangements that makes V. parahaemolyticus PCV08-7 a non-pandemic clone. We present detailed genome statistics and important genetic features of this bacterium and discuss how its survival, adaptation and virulence in marine and terrestrial hosts can be understood through the genomic blueprint and that the availability of genome sequence entailing this important Malaysian isolate would likely enhance our understanding of the epidemiology, evolution and transmission of foodborne Vibrios in Malaysia and elsewhere.
  10. Singh S, Bala MM, Kumar N, Janor H
    Int J Health Plann Manage, 2021 Jul;36(4):1236-1250.
    PMID: 33855765 DOI: 10.1002/hpm.3169
    This study assesses and compares the productive efficiency of the national healthcare system of the ASEAN region which includes Brunei, Cambodia, Indonesia, Laos, Malaysia, Myanmar, Philippines, Singapore, Thailand and Vietnam amidst rising mortality rate from noncommunicable diseases (NCDs) in the Sustainable Development Goals (SDGs) era. Nonparametric data envelopment analysis technique based on the Malmquist Productivity Index is performed and its components, total factor productivity change, technical change and technological change are compared across the region. Two different models are considered in assessing and comparing the technical efficiency of the national healthcare system across the region with life expectancy at birth and mortality rate from NCDs as parallel health care output for both the models. The mean value of total factor productivity is 0.983 and 0.974 which suggests that national healthcare system productivity efficiency decays by 1.7% for Model I and 2.6% for Model II, respectively. This suggests that the health care system inefficiencies across the ASEAN region have not made life expectancy to improve as much as it should be and curtailed the mortality rate from growing chronic NCDs within a decade. The region is likely to lag behind in achieving SDGs 3 target 4 on reducing by one-third premature mortality from chronic NCDs unless the health care system's technical efficiency is improved across the region. The finding suggests a microlevel study on each country to identify major sources of healthcare system inefficiency in a bid to ameliorate it.
  11. Singh AP, Prasad U, Kumar N
    Singapore Med J, 1983 Dec;24(6):367-73.
    PMID: 6681493
    Clinical synopsis and investigations on fourteen patients with blast injuries of the ear successfully treated at the ENT Unit of the University Hospital, Kuala Lumpur, revealed few interesting observations in addition to usual findings. The most outstanding one was the absence of sensorineural deafness, although it has been claimed as one of the most constant features. Conservative management alone was found to be of significant value.
  12. Sharma N, Khanna K, Kumar N, Karwasra R, Janakiraman AK, Rajagopal MS
    Assay Drug Dev Technol, 2023 Oct;21(7):325-330.
    PMID: 37801663 DOI: 10.1089/adt.2023.053
    An alternative to oral administration for the delivery of therapeutic substances is the topical route, which frequently has comparable efficacy but may have a better tolerability profile. Gamma scintigraphy is a noninvasive technique that involves the application of radioactive substances to conduct biodistribution studies of therapeutic substances delivered through various routes. Nimesulide (NSD) was radiolabeled with technetium pertechnetate (Technetium99m [99mTc]) and this radiolabeled drug complex (99mTc-NSD) was used to prepare a topical gel formulation. The permeation of the radiolabeled drug from the topical gel was determined by gamma scintigraphy on human volunteers. The region of interest was calculated for the quantification of permeated radiolabeled drugs. This was observed that the mean percentage permeation of 99mTc-NSD was found to be 0.32 ± 0.22 to 36.37 ± 2.86 at 5 and 240 min. It was demonstrated that gamma scintigraphy may be a noninvasive and reliable technique for the determination of drug permeation through topical routes.
  13. Satheesha Nayak B, Shetty SD, Sirasanagandla SR, Kumar N, Swamy Ravindra S, Abhinitha P
    Kathmandu Univ Med J (KUMJ), 2019 11 16;16(64):345-347.
    PMID: 31729351
    Celiac trunk is the first ventral branch of the abdominal aorta. It usually terminates by giving three branches; the common hepatic artery, the left gastric artery and the splenic artery. We report a rare variation of the branching pattern of the celiac trunk. The Celiac trunk divided into two branches; left gastric artery and splenicogastroduodenal trunk. The splenico-gastroduodenal trunk divided into splenic and gastroduodenal arteries. The superior mesenteric artery and hepatic artery took origin from a common hepato-mesenteric trunk. The hepatic artery had a winding course around the portal vein and hepatic duct. The knowledge of these variations is important while doing radiological investigations and liver transplant and pancreatic surgeries.
  14. Sampath Kumar NS, Sarbon NM, Rana SS, Chintagunta AD, Prathibha S, Ingilala SK, et al.
    AMB Express, 2021 Mar 01;11(1):36.
    PMID: 33646462 DOI: 10.1186/s13568-021-01194-9
    Psidium guajava L. (guava) is predominantly grown throughout the world and known for its medicinal properties in treating various diseases and disorders. The present work focuses on aqueous extraction of bioactive compounds from the guava leaf and its utilization in the formulation of jelly to improve the public health. The guava leaf extract has been used in the preparation of jelly with pectin (1.5 g), sugar (28 g) and lemon juice (2 mL). The prepared guava leaf extract jelly (GJ) and the control jelly (CJ, without extract) were subjected to proximate, nutritional and textural analyses besides determination of antioxidant and antimicrobial activities. GJ was found to contain carbohydrate (45.78 g/100 g), protein (3.0 g/100 g), vitamin C (6.15 mg/100 g), vitamin B3 (2.90 mg/100 g) and energy (120.6 kcal). Further, the texture analysis of CJ and GJ indicated that both the jellies showed similar properties emphasizing that the addition of guava leaf extract does not bring any change in the texture properties of jelly. GJ exhibited antimicrobial activity against various bacteria ranging from 11.4 to 13.6 mm. Similarly, GJ showed antioxidant activity of 42.38% against DPPH radical and 33.45% against hydroxyl radical. Mass spectroscopic analysis of aqueous extract confirmed the presence of esculin, quercetin, gallocatechin, 3-sinapoylquinic acid, gallic acid, citric acid and ellagic acid which are responsible for antioxidant and antimicrobial properties.
  15. Sambasivan M, Esmaeilzadeh P, Kumar N, Nezakati H
    PMID: 23216866 DOI: 10.1186/1472-6947-12-142
    Computer-based clinical decision support systems (CDSS) are regarded as a key element to enhance decision-making in a healthcare environment to improve the quality of medical care delivery. The concern of having new CDSS unused is still one of the biggest issues in developing countries for the developers and implementers of clinical IT systems. The main objectives of this study are to determine whether (1) the physician's perceived professional autonomy, (2) involvement in the decision to implement CDSS and (3) the belief that CDSS will improve job performance increase the intention to adopt CDSS. Four hypotheses were formulated and tested.
  16. Russo GI, Saleh R, Finocchi F, Juma AR, Durairajanayagam D, Kahraman O, et al.
    World J Mens Health, 2024 Feb 07.
    PMID: 38449451 DOI: 10.5534/wjmh.230260
    PURPOSE: Varicocele has been associated with high seminal oxidative stress (OS), impaired semen quality, and reduced male fertility potential. However, the exact mechanism(s) underlying the development of varicocele-mediated infertility and the cause-effect relationship between varicocele and testicular dysfunction are not fully understood. The aim of this systematic review and meta-analysis (SRMA) is to investigate the impact of varicocele on testicular OS markers and sperm parameters in experimental animals with varicocele as compared to animals without varicocele.

    MATERIALS AND METHODS: A literature search was performed using the Scopus and PubMed databases on studies that investigated testicular OS markers and sperm parameters in animals with varicocele. The primary outcomes included malondialdehyde (MDA) (nmol/mg) levels whereas the secondary outcomes included total sperm count (×106), sperm vitality (%), total sperm motility (%), and sperm DNA fragmentation (SDF) (%). Standardized mean difference (SMD) (95% confidence interval [CI]) was chosen to express the effect size. The quality of the included studies was evaluated using the Cambridge Quality Checklist.

    RESULTS: Out of 76 identified articles, 6 studies on rats were included in the meta-analysis. The analysis showed a significant increase of MDA (SMD: 15.61 [1.93, 29.29]; p=0.03) in rats with varicocele vs. controls. We also observed a significant decrease in total sperm count (SMD: -17.45 [-28.97, -5.93]; p<0.01), sperm vitality (SMD: -16.41 [-26.30, -6.52]; p<0.01), total sperm motility (SMD: -17.67 [-24.90, -10.44]; p<0.01), and a significant increase of SDF (SMD: 7.41 [1.23, 13.59]; p=0.02), in rats with varicocele vs. controls. The quality of the included studies was ranked as high.

    CONCLUSIONS: This SRMA indicates a significant increase in levels of testicular MDA and SDF and a reduction of sperm quality in experimental animals with varicocele. These findings support the potential role of testicular OS in the development of varicocele-induced testicular damage.

  17. Qureshi A, Syed Sulaiman SA, Rehman W, Mehmood A, Idrees S, Kumar N
    PLoS One, 2023;18(5):e0285736.
    PMID: 37220099 DOI: 10.1371/journal.pone.0285736
    BACKGROUND: The response to the vaccine may vary among individuals. Hence, it is important to know how often individuals experience side effects after immunization against COVID-19.

    OBJECTIVE: This study aimed to assess the incidence of side effects following COVID-19 vaccination across different vaccine recipients in Southern Pakistan and identify the potential factors associated with these side effects in the population.

    METHODS: The survey was conducted across Pakistan through Google-forms Links from August to October 2021. The questionnaire included demographic information and COVID-19 vaccine information. Chi-square (x2) was performed for comparative analysis to check the significance level with P <0.05. The final analysis included 507 participants who had received COVID-19 vaccines.

    RESULTS: Of the total 507 COVID-19 vaccines recipients, 24.9% received CoronaVac, 36.5% received BBIBP-CorV, 14.2% received BNT162b2, 13.8% received AZD1222, and 10.7% received mRNA-1273. The most prominent side effects after the first dose were fever, weakness, lethargy, and pain at the site of injection. Moreover, the most commonly reported side effects after the second dose were pain at the injection site, headache, body ache, lethargy, fever, chills, flu-like symptoms, and diarrhea.

    CONCLUSION: Our results suggested that the side effects due to COVID-19 vaccination can vary between the first and second doses and type of COVID-19 vaccine. Our findings suggest continuing monitoring of vaccine safety and the importance of individualized risk-benefit assessment for COVID-19 immunization.

  18. Qureshi A, Syed Sulaiman SA, Kumar N, Qureshi PAAA
    PLoS One, 2022;17(7):e0270761.
    PMID: 35793377 DOI: 10.1371/journal.pone.0270761
    Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-1), notoriously known as COVID-19, emerged in 2019 and was responsible for causing acute respiratory collapse. Moreover, in September 2020, new variant cases of severe acute respiratory syndrome coronavirus 2 were reported in the United Kingdom, with many patients and deaths. This study aimed to see knowledge, perception, and fear among the global population towards a new variant of severe acute respiratory syndrome coronavirus 2, known as Omicron (B.1.1.529). This online cross-sectional global study was conducted during the emergence of the B.1.1.529 variant, also known as the Omicron variant. The survey was carried out from 2nd December 2021 to 3rd January 2022. The descriptive analysis was presented as frequencies (N), percentages (%), and mean ± standard deviation (m ± SD). The association between dependent and categorical independent variables was determined using the Chi-square test (x2). Statistical analysis was performed by using SPSS version 23. Of 353 respondents, approximately 61% were females. One hundred fifty-four respondents were in the age group of 18-27 years. The average age was 31.53±10.3 (mean± SD). The majority of respondents (43.9%) were from Indonesia. The mean knowledge score about the Omicron variant was 3.18±1.14. Our study suggests that people have some knowledge about the new variant, Omicron (B.1.1.529). Besides, there was a significant association (p = 0.05) for the perception of the fatality rate of Omicron among the respondents from different countries. However, there is still an ample research gap in enlightening people about this infection (B.1.1.529).
  19. Padur AA, Kumar N
    J Vasc Bras, 2019 Jul 12;18:e20190021.
    PMID: 31360158 DOI: 10.1590/1677-5449.190021
    The facial artery is the main artery of the face and variations in its origin and its branching pattern have been documented. We report herein multiple facial artery branch variations in the face. A large posterior (premasseteric) branch originated from the left facial artery and coursed upwards behind the main trunk of the facial artery. This artery presented with a straight course and was closely related to the anterior border of the masseter. The branch then terminated by supplying the adjacent connective tissue below the parotid duct. It was also observed that the facial artery was very thick and tortuous and terminated as the superior labial artery. Knowledge of this variation is of great clinical significance in facial operations, especially for maxillofacial surgeons and plastic surgeons, because it forms the anatomical basis for the facial artery musculo-mucosal flap.
  20. Nayak SB, Kumar N, Sirasanagandla SR, Srinivas SP, Pamidi N, Shetty SD
    Anat Cell Biol, 2018 Jun;51(2):136-138.
    PMID: 29984059 DOI: 10.5115/acb.2018.51.2.136
    Osteochondromas develop as cartilaginous nodules in the periosteum of bones. They are the commonest benign tumors of the skeleton, generally observed in the long bones. Rarely, they are also found in the axial skeleton, flat bones of skull and facial bones. During a regular dissection, we came across a solitary osteochondroma in posterior surface of the body of the right pubic bone. Histopathology of the bony projection confirmed the typical features of the osteochondroma. The symptomatic osteochondromas are usually evaluated during radiographic examination. Though, the observed osteochondroma is relatively smaller its unusual location is remarkable and knowledge of occurrence of such nodules is clinically important during the diagnosis and planning of treatment.
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