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Biomedical subjects

P K Das

Publications and source records attributed to P K Das.

At least 19 recordsLinked to original sources

Polymorphism of gp15/400 allergen gene of Wuchereria bancrofti from different regions of India endemic for lymphatic filariasis.

Nematode polyprotein allergens (NPA) are lipid-binding/transport molecules that elicit elevated levels of IgE response in the infected host, leading to Th2 type of immune response. They also transport arachidonic acid and metabolites that is known to be the action of antifilarial drug, diethylcarbamazine, and hence are of great significance to the control of lymphatic filariasis. We investigated the polymorphism of gp15/400 polyprotein of 35 isolates of lymphatic filarial parasite Wuchereria bancrofti collected from different geographic locations of India. The repeat subunit of the gene was found to be highly conserved in all the isolates with only two nucleotide synonymous changes at positions 369 (A-G) and 375 (C-T). As this molecule is highly conserved and has multifarious roles in the survival and pathogenesis of the parasite, it has good potential as a target for drug, immunodulation tools and immunotherapy development.

Allergens↗

Polymorphism of gp15/400 allergen gene of W. bancrofti from different regions of India endemic for lymphatic filariasis.

Nematode polyprotein allergens (NPA) are lipid binding/transport molecules that elicit elevated levels of IgE response in the infected host, leading to Th2 type of immune response. They also transport arachidonic acid and its metabolites that are known to be involved in the action of antifilarial drug, Diethylcarbamazine and hence are of great significance for the control of lymphatic filariasis. We investigated the polymorphism of gp15/400 polyprotein of 35 isolates of lymphatic filarial parasite Wuchereria bancrofti collected from different geographic locations of India. The repeat sub-unit of the gene was found to be highly conserved in all the isolates with only two nucleotide synonymous changes at positions 286 (A-G) and 337 (C-T). Since this molecule is highly conserved and has multifarious roles in the survival and pathogenesis of the parasite it has good potential as a target for drug, immunodulation tool and immunotherapy development.

Allergens↗

Changes in Wuchereria bancrofti infection in a highly endemic community following 10 rounds of mass administration of diethylcarbamazine.

Mass drug administration (MDA) is the principal strategy of the programme to eliminate lymphatic filariasis (LF). Evaluation of MDA in highly endemic 'sentinel' communities is necessary to understand its impact on LF infection. This study examined the changes in Wuchereria bancrofti infection following 10 rounds of annual mass administration of diethylcarbamazine (DEC) in a highly endemic community. The mean number of DEC treatments received per adult in the community was 7.4+/-2.0. Following 10 rounds of DEC administration, the number of microfilaria (mf) carriers fell from 565 to 55. None of the pre-MDA amicrofilaraemic individuals showed circulating filarial antigen (CFA). However, 54.5% of the pre-MDA microfilaraemic individuals were positive for CFA. All the pre-MDA high intensity mf carriers continued to be positive for CFA, and some of them also showed blood mf. These patients are the most difficult to be cured by MDA and were distributed in 8.2% of the households. All the children born during the last 7 years of the MDA programme were negative for CFA. The study suggests that six to seven DEC treatments per individual suppresses microfilaraemia, except in some people with heavy infection, and repeated MDA has very good potential to prevent infection in children.

Adult↗

Protection from experimental colitis by theaflavin-3,3'-digallate correlates with inhibition of IKK and NF-kappaB activation.

BACKGROUND AND PURPOSE: Inflammatory bowel disease (IBD) is associated with activation of nuclear factor kappa B (NF-kappaB) involved in regulating the expression of inducible nitric oxide synthase (iNOS) and proinflammatory cytokine genes. As theaflavin-3,3'-digallate (TFDG), the most potent anti-oxidant polyphenol of black tea, down-regulates NF-kappaB activation, we investigated if TFDG is beneficial in colonic inflammation by suppressing iNOS and proinflammatory cytokines. EXPERIMENTAL APPROACH: The in vivo efficacy of TFDG was assessed in mice with trinitrobenzene sulfonic acid (TNBS)-induced colitis. Both mRNA and protein levels of proinflammatory cytokines and iNOS were analyzed in colon tissue treated with or without TFDG. NF-kappaB activation was determined by electrophoretic mobility shift assay and levels of NF-kappaB inhibitory protein (IkappaBalpha) were analyzed by Western blotting. KEY RESULTS: Oral administration of TFDG (5 mg kg(-1) daily i.g.) significantly improved TNBS-induced colitis associated with decreased mRNA and protein levels of TNF-alpha, IL-12, IFN-gamma and iNOS in colonic mucosa. DNA binding and Western blotting revealed increase in NF-kappaB activation and IkappaBalpha depletion in TNBS-treated mice from Day 2 through Day 8 with a maximum at Day 4, which resulted from increased phosphorylation of IkappaBalpha and higher activity of IkappaB kinase (IKK). Pretreatment with TFDG markedly inhibited TNBS-induced increases in nuclear localization of NF-kappaB, cytosolic IKK activity and preserved IkappaBalpha in colon tissue. CONCLUSIONS AND IMPLICATIONS: TFDG exerts protective effects in experimental colitis and inhibits production of inflammatory mediators through a mechanism that, at least in part, involves inhibition of NF-kappaB activation.

Animals↗

Isolation of Wuchereria bancrofti microfilariae from archived stained blood slides for use in genetic studies and amplification of parasite and endosymbiont genes.

Information on change in genetic diversity of Wuchereria bancrofti is important in view of the launching of the Global Lymphatic Filariasis Elimination Programme, as it may have important consequences on the control operations and on the potential resurgence after their withdrawal. Since attention was not paid to generate such information when the programme was launched, use of archived parasite material will provide an opportunity to derive this information in a prospective manner. In this paper a simple and effective technique is reported for isolation of microfilariae of W. bancrofti from dried and stained slides archived for several years and their utility in analysis of genetic structure and amplification of certain genes of the parasite is tested. The method was found to be efficient in purifying mf from the dried smears and the DNA of the parasite found to be useful in studying the genetic structure of Wuchereria bancrofti populations using random amplified polymorphic DNA (RAPD)-PCR and for amplifying genes of the parasite and its endosymbiont, Wolbachia sp.

Animals↗

Effect of food on immature development, consumption rate, and relative growth rate of Toxorhynchites splendens (Diptera: Culicidae), a predator of container breeding mosquitoes.

Food utilization by the larvae of Toxorhynchites splendens (Wiedemann) was studied in the laboratory by offering larvae of Aedes aegypti Linnaeus, Anopheles stephensi (Liston), and Culex quinquefasciatus (Say). Quantitative analyses of data indicated that immature development was significantly faster with increase in food availability. The regression analysis showed that the degrees of the relationship between immature duration (Id) and food availability were higher when offered early instars of prey (first and second instars) than late instars. Consumption rate (Cr) of the predator increased with increase in food availability and this relationship was highly significant when larvae of An. stephensi were offered as food. Consumption rate to food level decreased with increase in the age class of the prey. There was a significant negative correlation between Id and Cr. This aspect helps to increase population turnover of T. splendens in a shorter period when the prey is abundant. Conversely, the predator compensated the loss in daily food intake at low food level by extending Id thereby attains the minimum threshold pupal weight for adult emergence. There was an increase in the relative growth rate (RGR) of the predator when An. stephensi was offered as prey and this was related to the high protein content of the prey per body weight. There was a positive correlation between Cr and RGR. This adaptive life characteristic strategy of this predator is useful for mass-rearing for large scale field release programmes in the control of container breeding mosquitoes is discussed.

Animals↗

Phylogeography of human lymphatic filarial parasite, Wuchereria bancrofti in India.

Wuchereria bancrofti, a nematode parasite causing human lymphatic filariasis is widely distributed in India. The phylogeography of this parasite was studied by constructing RAPD profiles of parasite populations collected from 71 microfilaria carriers residing in different geoclimatic regions of India. The analysis showed that the phylogeography of W. bancrofti populations is complex, with a high genetic divergence and gene flow among populations. The total genetic diversity (H(T)) and genetic differentiation (G(ST)) estimated for all the parasite populations were 0.0926 and 0.5859, respectively. The gene flow (Nm) between different regions indicated that two strains of W. bancrofti were prevalent in the country, one in the eastern side and the other on the western side of the Western Ghats. A highly significant genetic differentiation (F(ST) [theta] = 0.7978) was estimated between these two strains (chi 2 = 308.2789; P < 0.001). The gene flow between these strains was very low (0.2338). These two strains appear to have drifted genetically because of their geographic isolation by this thickly forested mountain range. The strain in the eastern side was found to be monophyletic in origin and is undergoing genetic divergence as the major parasite population in the country, spanning from eastern peninsular region to the northern plains. The variable geoclimatic factors and the antifilarial chemotherapeutical pressure on the parasite, which is in place for the past half a century, might have contributed for the high genetic heterogeneity its strains/populations in the country. The route of entry of the parasite into Indian sub-continent possibly appeared to be from an ancient origin from the countries of the Southeast Asian archipelago, through the eastern coastal line of the southern peninsula.

Animals↗

Operational feasibility of lot quality assurance sampling (LQAS) as a tool in routine process monitoring of filariasis control programmes.

Lot quality assurance sampling (LQAS) with two-stage sampling plan was applied for rapid monitoring of coverage after every round of mass drug administration (MDA). A Primary Health Centre (PHC) consisting of 29 villages in Thiruvannamalai district, Tamil Nadu was selected as the study area. Two threshold levels of coverage were used: threshold A (maximum: 60%; minimum: 40%) and threshold B (maximum: 80%; minimum: 60%). Based on these thresholds, one sampling plan each for A and B was derived with the necessary sample size and the number of allowable defectives (i.e. defectives mean those who have not received the drug). Using data generated through simple random sampling (SRSI) of 1,750 individuals in the study area, LQAS was validated with the above two sampling plans for its diagnostic and field applicability. Simultaneously, a household survey (SRSH) was conducted for validation and cost-effectiveness analysis. Based on SRSH survey, the estimated coverage was 93.5% (CI: 91.7-95.3%). LQAS with threshold A revealed that by sampling a maximum of 14 individuals and by allowing four defectives, the coverage was >or=60% in >90% of villages at the first stage. Similarly, with threshold B by sampling a maximum of nine individuals and by allowing four defectives, the coverage was >or=80% in >90% of villages at the first stage. These analyses suggest that the sampling plan (14,4,52,25) of threshold A may be adopted in MDA to assess if a minimum coverage of 60% has been achieved. However, to achieve the goal of elimination, the sampling plan (9, 4, 42, 29) of threshold B can identify villages in which the coverage is <80% so that remedial measures can be taken. Cost-effectiveness analysis showed that both options of LQAS are more cost-effective than SRSH to detect a village with a given level of coverage. The cost per village was US dollars 76.18 under SRSH. The cost of LQAS was US dollars 65.81 and 55.63 per village for thresholds A and B respectively. The total financial cost of classifying a village correctly with the given threshold level of LQAS could be reduced by 14% and 26% of the cost of conventional SRSH method.

Adolescent↗

A campaign of "communication for behavioural impact" to improve mass drug administrations against lymphatic filariasis: structure, implementation and impact on people's knowledge and treatment coverage.

In the mass drug administrations (MDA) that form the principal strategy of the Global Programme to Eliminate Lymphatic Filariasis, treatment coverages of at least 65%-80% will be needed if the programme is to be successful. In the Indian state of Tamil Nadu, where treatment coverages were typically <65%, a comprehensive strategy of advocacy and communication, called the "communication for behavioural impact" (COMBI) campaign, has been developed and implemented, in an attempt to improve treatment coverage. This strategy combined advocacy, aimed at state-, district- and village-level administrations, with communication activities targeted at individual communities. The main aim was to alter the behaviour of many of those included in the rounds of MDA, so that they would be more likely to accept and consume the diethylcarbamazine tablets offered to them. The COMBI campaign had two variants, COMBI(+) and the more intensive COMBI(+ +), each of which has been implemented in six districts. Both the variants included the "personal selling" of treatment, via door-to-door visiting by a total of 113,500 filaria-prevention assistants. These assistants were able to visit 34%-49% of the households in each target community. In the COMBI(+ +) districts, up to 44% and 38% of households received information on lymphatic filariasis and its elimination via television commercials and posters, respectively. Overall, 78% of the villages in the COMBI(+ +) districts and 33% of those in the COMBI(+) districts were considered to have had good exposure to the communication campaign. At the end of this campaign about 30% more people (than pre-campaign) believed that lymphatic filariasis could be eliminated and many of those targeted considered lymphatic filariasis to be a dreadful disease, knew that a particular day had been designated "Filaria Day", and thought that the tablets offered in MDA should be consumed to prevent or eliminate the disease. Apparently as the result of the COMBI campaign, drug consumption increased, from 33% of those living in endemic communities, to 37% in the COMBI(+) districts and to 49% in the COMBI(+ +). Coverages as high as 65%-73% were recorded among those who had had the maximum exposure to the communication campaign. These results indicate that the COMBI campaign favourably changed the perception and behaviour of the people towards the elimination of lymphatic filariasis. The costs of the COMBI(+) and COMBI(+ +) strategies were only U.S.$0.002 and U.S.$0.009 per capita, respectively.

Attitude to Health↗

Population interactions between Culex vishnui mosquitoes and their natural enemies in Pondicherry, India.

Population interactions among mosquitoes in the Culex vishnui subgroup, which are vectors of Japanese Encephalitis, and their natural enemies were studied in Pondicherry, India. We tested the hypothesis that the breakdown of interactions between the larvae and their natural enemies due to drought followed by rain was responsible for the sudden increase in the vector population above the threshold for disease transmission during the heavy rainy period. We randomly sampled mosquito larvae and their predators in different breeding habitats and subjected the mean densities of prey, predator, and mosquito larvae infected with parasites/pathogens to covariate analysis to understand the interaction between prey and their natural enemies in relation to environmental factors. In rice fields, neither prey nor predator showed any positive correlation with temperature, RH, or the number of rainy days. However, the pathogen/parasite of mosquito immatures showed a positive correlation with RH. Among the mosquito predators, notonectids exhibited a significant positive correlation with Cx. vishnui larvae. The parasitic Romanomermis iyengari and pathogenic Coelomomyces anopheliscus also showed positive correlations with immatures. No parasites and pathogens of mosquito larvae were recorded in shallow water pools (SWP) or cement tanks (CT) during the study period. Important predators recorded in SWP were notonectids, damselfly nymphs, Diplonychus indicus, and hydrophilids. Dragonfly nymphs, gerrids, and tadpole shrimps were recorded in CT. In CT, prey and their predators were positively correlated with RH and rainy days. In SWP, there was a highly significant correlation between prey, predators and environmental factors. We conclude that rice fields are a stable ecosystem where regular interaction occurs between larvae and their natural enemies and a sudden increase in mosquito populations is uncommon. In transient habitats, no such stability is present and they become more important as breeding habitats in terms of seasonality and number. Shallow water pools should be seriously considered for the control of these vectors.

Animals↗

Extension of the intensive phase reduces unfavourable outcomes with the 8-month thioacetazone regimen.

SETTING: Damien Foundation tuberculosis (TB) control projects in Bangladesh. OBJECTIVE: To assess the effectiveness of a 1-month extension of the intensive phase for smear-positives at 2 months of an 8-month regimen with a continuation phase consisting of isoniazid (INH) and thioacetazone (Th). DESIGN: A prospective study of two cohorts of newly registered smear-positive cases, with extension of the intensive phase for the control cohort, but not for the study cohort. Culture and drug susceptibility testing (DST) of smear-defined failures and relapses and of random samples of new cases. RESULTS: Among 8230 study patients (86.7% 2-month conversion) and 7206 controls (83.4% conversion), smear-defined failure or relapse outcome was 3.0% for 2-month smear-negatives vs. 3.1% for 2-month smear-positives with extension (non-significant, NS), and 8.2% for 2-month smear-positives with no extension (P < 0.00001). Culture-confirmed failure and relapse reached 1.9% in 2-month smear-negatives and 1.6% (NS) in 2-month smear-positives with vs. 3.7% (P < 0.001) in 2-month smear-positives with no extension. The relative risk (RR) of non-extension in 2-month smear-positives was 2.4 (cultures) to 2.7 (smears). The same RR and borderline significance was found for non-extension of patients with pan-susceptible strains. CONCLUSIONS: Extension of the intensive phase considerably reduces failures and relapses with a weaker regimen in patients smear-positive at 2 months. Its effectiveness may vary with extent of initial drug resistance vs. power of the regimen.

Antitubercular Agents↗

Diversity and divergence among the tribal populations of India.

Tribal populations of the Indian subcontinent have been of longstanding interest to anthropologists and human geneticists. To investigate the relationship of Indian tribes to Indian castes and continental populations, we analyzed 45 unlinked autosomal STR loci in 9 tribal groups, 8 castes, and 18 populations from Africa, Europe and East Asia. South Indian tribal populations demonstrate low within-population heterozygosity (range: 0.54 - 0.69), while tribal populations sampled further north and east have higher heterozygosity (range: 0.69 - 0.74). Genetic distance estimates show that tribal Indians are more closely related to caste Indians than to other major groups. Between-tribe differentiation is high and exceeds that for eight sub-Saharan African populations (4.8% vs. 3.7%). Telugu-speaking populations are less differentiated than non-Telugu speakers (F(ST): 0.029 vs. 0.079), but geographic distance was not predictive of genetic affinity between tribes. South Indian tribes show significant population structure, and individuals can be clustered statistically into groups that correspond with their tribal affiliation. These results are consistent with high levels of genetic drift and isolation in Indian tribal populations, particularly those of South India, and they imply that these populations may be potential candidates for linkage disequilibrium and association mapping.

Asia↗

A new therapeutic approach to treat psoriasis by inhibition of fatty acid oxidation by Etomoxir.

BACKGROUND: The dogma in psoriasis is that due to pathogen-induced inflammatory responses, an autoreactive immune response is induced that leads to tissue destruction. However, this model might be too simplistic. Literature data suggest that the expression of enzymes crucial for fatty acid oxidation is upregulated in the skin of patients with psoriasis compared with healthy individuals. OBJECTIVES: To examine the influence of fatty acid oxidation on psoriasis with regard to expression and activity of the key enzyme in fatty acid oxidation, carnitine palmitoyltransferase-1 (CPT-1) and the effect of the CPT-1 inhibitor, Etomoxir. METHODS: Experiments were performed with homogenates of lesional and healthy skin, fibroblast cultures and a model of human psoriatic skin transplanted on immune-deficient BNX mice. RESULTS: CPT-1 was highly active in lesional skin. Etomoxir was able to block CPT-1 activity in skin, implying that this antagonist may have the potential to suppress psoriasis when administered topically. In the mouse model, Etomoxir had an antipsoriatic effect that was at least as good as that of betamethasone, as evidenced by reduction of epidermal thickness, keratinocyte proliferation and differentiation. CONCLUSIONS: We conclude that fatty acid metabolism and in particular CPT-1 may be an excellent target for treatment of psoriasis.

Animals↗

DDT indoor residual spray, still an effective tool to control Anopheles fluviatilis-transmitted Plasmodium falciparum malaria in India.

This study from two districts of Orissa State which are endemic for Plasmodium falciparum transmitted by Anopheles fluviatilis and A. culicifacies investigated the impact of dichlorodiphenyl trichloroethane (DDT) indoor residual spraying, in view of the ongoing discussion on phasing out DDT in India. Based on their high annual parasite incidence and logistical considerations, 26 villages in Malkangiri and 28 in Koraput district were selected for DDT spraying. For comparison, six and four unsprayed villages were chosen from the same districts. In each district, the prevalence of malaria infection and incidence of malaria fever, indoor resting density and parous rate of the vectors, and their susceptibility to DDT were monitored in six and three villages selected randomly from the sprayed and unsprayed groups respectively. Anopheles fluviatilis was susceptible to DDT while A. culicifacies was resistant. DDT residual spraying with 1 g/m(2), was carried out in October-November 2001. Spraying 74-86% of human dwellings and 100% of cattle sheds brought down the indoor resting density of A. fluviatilis by 93-95%. This was associated with a significant reduction of incidence of malaria fever as well as prevalence of malaria infection from November to February in both districts. The spraying also seemed to impact on vector longevity, and a residual effect of DDT on the sprayed walls was observed up to 10-12 weeks despite re-plastering. Hence DDT spraying can still be an effective tool for controlling fluviatilis-transmitted malaria. Although this species is exophilic, its nocturnal resting behaviour facilitates its contact with the sprayed surfaces. DDT is still useful for residual spraying in India, particularly in areas where the vectors are endophilic and not resistant.

Animals↗

Pattern of community compliance with spaced, single-dose, mass administrations of diethylcarbamazine or ivermectin, for the elimination of lymphatic filariasis from rural areas of southern India.

Current programmes to eliminate lymphatic filariasis (LF) are largely based on annual mass administrations of single doses of antifilarial drugs. The level and pattern of compliance by the target population are important determinants of the success of such mass drug administrations (MDA). Community compliance was therefore investigated during a study in southern India of the effects, on Wuchereria bancrofti microfilaraemia and transmission, of spaced MDA based on diethylcarbamazine (DEC) or ivermectin (IVM). During six rounds of MDA, the frequency of compliance in the target populations, in the five study villages given DEC and the five given IVM, ranged from 55%-77%. Analysis of the relevant cohort data indicated that about 30% of the villagers had complied with treatment during all six rounds, but 3.5% of those in the DEC arm and 4.0% of those in the IVM arm had never complied with treatment. Most of the villagers (>90%) had received treatment at least once, however, and >60% had each received treatment in at least four of the six rounds. Overall, there was a significant negative correlation (r=-0.78; P=0.008) between the size of the village, in terms of the number of villagers, and the mean frequency of compliance over the six rounds of MDA. The pattern of community compliance was found to be 'semi-systematic', laying between random and systematic. In terms of the elimination of LF, a semi-systematic pattern of compliance is worse than random compliance but better than systematic. The relevance of the levels and patterns of compliance to LF control or elimination is discussed.

Animals↗

Situation analysis in a large urban area of India, prior to launching a programme of mass drug administrations to eliminate lymphatic filariasis.

The main strategy now adopted for the elimination of lymphatic filariasis (LF) is based on mass drug administrations (MDA). Annual administration of antifilarial drugs to 65%-80% of the population at risk of the disease is believed to be necessary if LF is to be eliminated, at least as a public-health problem, within a reasonable time-frame. To facilitate the development of drug-delivery strategies that are sufficient to ensure such high treatment coverages in large urban areas, a situation analysis was undertaken in the Indian city of Chennai. The subjects interviewed came from households with high, moderate, low or very low incomes. A lack of information on the prevalence and socio-economic impact of the disease meant that LF was not viewed as a major pubic-health problem in the study area, even though cases of elephantiasis and hydrocele were detected in 2%-8% and 7%-20% of the households investigated. Overall, 40% of the interviewees from very-low-income households and 78% of those from middle-income households knew that (the parasite causing) elephantiasis was transmitted by mosquitoes. Only 4% of the subjects from high-income areas and 1% of those from low-income areas were aware that filarial infection was a major cause of hydrocele. Most of the subjects (>55% of each of the four socio- economic groups considered) felt that they were not at risk of developing elephantiasis. When specifically asked, only 35% of the subjects from high-income households but 84% of those from low-income households said that they would be willing to consume tablets of an antifilarial drug (diethylcarbamazine) in MDA to eliminate LF. It is therefore unclear whether high-income households in urban areas should be included in MDA programmes. The interviewees felt that an intensive campaign of information, education, communication and advocacy would be necessary if an effective MDA-based programme were to be implemented. Drug distribution through the health services was the most preferred option.Clearly, factors such as a lack of appreciation of the socio-economic impact of LF, a general belief that the risk of elephantiasis is low, doubts about the need to include all sectors of the eligible population in MDA, and a common dependence on private practitioners make successful MDA against LF in urban areas a challenging task. On the positive side, however, an urban population is often covered by a huge network of colleges, private practitioners, non-governmental organizations and residents' associations, and such networks provide new opportunities in the development of effective drug-delivery strategies.

Animals↗

Studies on sodium and potassium metabolism and subsequent influence on electrocardiogram in unilaterally adrenalectomized black Bengal goat (Capra hircus).

Unilateral adrenalectomy was performed in six black Bengal goat (Capra hircus)to study electrocardiograph in connection with mineral metabolism with special reference to sodium and potassium and some other factors of physiological importance. The parameters were studied at every 12 hrs interval upto 120 hrs and 24 hrs interval from 120 to 240 hrs. Physiological parameters, like body weight and rectal temperature, changed non-significantly (p < 0.05) after adrenalectomy. Among minerals, plasma sodium (p < 0.01) and plasma potassium (p < 0.05) concentration were changed significantly between hours leaving impression in ECG as widening of QRS complex and peaked T wave with increased amplitude found after unilateral adrenalectomy. Heart rate also increased significantly (p < 0.01) between hours.

Adrenalectomy↗