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Corona mortis (CMOR) is an anastomotic channel either arterial, venous or both connecting the obturator and external iliac systems excluding aberrant channels in the retropubic space. The goal of this study is to illustrate the type of CMOR via the Anterior Intrapelvic approach (AIP) which has not been studied in tandem. This descriptive observational study was performed in the Department of Anatomy, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India from January 2018 to December 2020. It is a potential culprit for significant haemorrhage in scenarios of pelvic trauma or when sectioned accidentally, augmenting difficult haemostasis behind the superior pubic ramus. Previously reported to be exclusively arterial, the venous variant has now emerged as the more frequent anastomosis. AIP was performed on 31 adult human cadavers of 62 hemipelvises to record variations and statistical analysis of retropubic anastomosis with respect to gender, weight groups and side distribution was done. Corona Mortis was observed in 50(80.6%) hemipelvises. To ramify, venous CMOR and arterial CMOR were exclusively encountered in 25(40.3%) and 10(16.10%) hemipelvises respectively. Males recorded a higher prevalence of CMOR. Despite being a frequent anastomotic variant, it is a rare entity in textbooks. CMOR can potentially alter patient outcome and have serious implications in pelvic surgeries via AIP owing to its easier accessibility. Besides, venous CMOR being more common, a venous bleed is inherently more arduous to manage in the pelvis. A larger calibre, less frequent aberrant channel could also prove to be lethal in its injury. Hence, cadaveric simulation of the technique is paramount to master the technique and to mitigate catastrophic vascular events.

Existence of variations in morphological proportions in human beings has led to the development of different values of tibio femoral angle (TFA) in different populations which is undoubtedly useful in clinical orthopaedic surgery. Meagre literature is available among Indian population. The cross-sectional study was creating baseline data of TFA among Rajasthani population of India with reasonable accuracy and also to correlate these data to radiological findings during July 2014-June 2016. The TFA (in degrees) of 500 healthy subjects from various regions of Rajasthan were measured in standing and supine positions. In addition, the TFA of 134 persons (randomly selected) from study group were also measured on roentgenogram. Subsequently both of these data were compared. The normal range of TFA angle in Rajasthani population was in between 160°-174°. TFA in standing position on right side was 170.96° (with 95% Confidence Interval (CI) = 170.24 to 171.68) and on left side was 170.14° (with 95% CI = 169.21 to 171.06). Mean TFA in supine position on right side in age group from 21 to 30 years was 167.12±6.73° and in age group from 31-40 years was 167.668±6.7°. No significant difference was observed in posture change and according to age. Statistically significant difference was observed in between radiological and gross measurement which was more in radiological than to clinical measurement of TFA (mean difference = +5.78° units) with 95% CI for the difference is (4.03°-7.53°). Higher values of tibio-femoral angle (TFA) were observed in males as compared to females and in radiological measurements.

Carrying angle is one of the secondary sexual characteristics which is important for keeping the hand away from body to improve functionality. A cross-sectional survey was conducted in Western Indian population (rural and urban population in and around Jodhpur district) during July 2014-June 2016 with the purpose of evaluating the carrying angle in apparently healthy adult and determines the range of normality according to age, sex, height, waist circumference and special reference to handedness. The carrying angle (elbow) was measured in 504 adults aged between 20-40 years (by simple random sampling) by a digital Goniometer. The subjects were in anatomical position (stand up straight, roll his/her shoulders back and the elbow was fully extended and the forearm fully supinated) while the carrying angle were taken. Carrying angle of the right side in male's 11.54°±1.29° and in female's 13.41°±1.26°, whereas these value in left side 10.21°±1.34° and 12.19°±1.44° respectively. All measurements in females are significantly higher in comparison to males (p0.001). The significant difference was observed in carrying angle according to handedness; dominant hand had higher value of carrying angle in comparison to non-dominant hand in both gender (p0.001). The height of individuals is positively correlated with the angle whereas there was no correlation was found in between age, waist circumference. The present study showed that the females have greater carrying angle than males.

Infertility is a growing health problem. It affects relatively large number of couples both globally as well as in India. Fertility treatment registers suggest that infertility is on increase. With the advancement in the knowledge and technology about the In Vitro fertilization (IVF) process, In Vitro fertilization success rates are improving over the time. In many cases of male-factor infertility, Intracytoplasmic sperm injection (ICSI) is the recommended treatment. The aim of this study was to estimate fertilization, implantation and pregnancy rates in ICSI cycles in association with number of attempts and sperm morphology. A total of 250 IVF-ICSI cycles were performed at a Fertility Center in Jaipur, Rajasthan, India. This cohort study was performed during 2013 to 2015. The differences in the outcomes of ICSI in association with sperm morphology and number of ICSI attempt were evaluated. Significantly higher mean was observed in fertilization rate and live birth rate with ≥5% sperm morphology 79.63% vs. 71.46% and 20% vs. 13.9% respectively). Significantly higher mean implantation rate and clinical pregnancy rate (CPR) and live birth rate were observed with attempt 3 as compared to 1 and 2 attempts. IVF success rates are improving over the time as knowledge and technology are advancing. Sperm morphology and number of attempt affect the ICSI outcomes.

Background Lesions of the sinonasal area are varied, but they mostly present as polypoid masses which require meticulous work-up to reach at the most probable diagnosis. Objective Analysis of polypoid sinonasal masses in terms of etiology, clinical presentations, brief demographic profile, clinico-histologic correlate where possible, and follow-up results. Method In this descriptive, longitudinal study, 198 patients with polypoid sinonasal masses attending the otolaryngology clinic of a tertiary teaching institute were selected using proper selection criteria and analyzed through a pre-set proforma and algorithm for a diagnostic work-up (that included histopathology where necessary). Result Common presentations were nasal obstruction (~89%), discharge (~70%) and hyposmia (~22%). Though nearly 87% was clinically benign and 8% indeterminate, therapeutic and diagnostic interventions (including histopathology) showed 91% truly benign, of which polyposis formed the bulk. Sensitivity of clinical detection was 75% for benign lesions and 62% for malignancies. Diagnosis depended on histopathology in 52.52% cases, including the clinically malignant, the "grey zone", and more than 40% of the clinically benign lesions. There was male predilection (2.16 for benign lesions and 1.57 for malignant), rural preponderance, and above 60% of the patients were within 50-70 years. There was ~26% recurrence in the follow-up period of a minimum of one year, predominantly in polyposis (29.55%) and malignancies (~39%). Conclusion Presentations of polypoid sinonasal masses are variable, etiology of which is mostly benign. Proper clinico-histologic correlate is necessary for correct diagnosis. A low threshold of suspicion is required because of this variability, necessitating follow-up for further evaluation.

PREVIOUS histological and experimental investigations have suggested a close pathogenetic relationship between the reticulo-endothelial system (RES) and amyloidosis1–3. The two-phase cellular theory2 considers the reticular cells and the plasma cells originating from them to be of aetiological importance in the formation of amyloid. The shift from pyroninophilia to periodic acid–Schiff positivity in the cells is believed to represent the morphological equivalent of exhaustion of the RES which leads to amyloid development. Our functional studies4 on experimental amyloidosis have revealed a strain dependent increase with phagocytic activity of the RES during the late preamyloid stage, followed by a return to the normal state at the time of the first deposition of amyloid. Attempts to influence experimental amyloidosis by alteration of the activity of the RES by carbon “blockade”5,6, as well as its increase by castration, seem to inhibit the formation of amyloid7. Increased amyloid formation has been induced by treatment with colloidal gold8.

Experimental infection of golden hamsters with the hookworm, Ancylostoma ceylanicum, caused a profound decline in the hepatic microsomal cytochrome P450 content. Concomitant decrease was also noticed in aminopyrine N-demethylase and benzo[a]pyrene hydroxylase activities. However, aniline hydroxylase activity was only marginally elevated during the infection. Microsomal markers, viz., cytochrome b5, NADH-cytochrome-c reductase, and glucose-6-phosphatase, were not significantly altered. Hepatic tissue exhibited an accumulation of lipids, especially phospholipids, triglycerides, and cholesterol, resulting in fatty necrosis around the central vein region. Isolated hepatic microsomes showed a decrease in phosphatidylcholine content. Impairment in hepatic mixed function oxidase (MFO) activities was further confirmed by prolongation in hexobarbital sleeping time and zoxazolamine-induced paralysis. The hepatic MFO system of A. ceylanicum-infected hamsters responded qualitatively and quantitatively in a manner similar to that of control hamsters, upon stimulation with selective chemical inducers like phenobarbitone and 3-methylcholanthrene. Kinetic and in vitro substrate binding studies revealed that for aminopyrine the substrate affinity and the maximum enzyme activity (Vmax) were decreased, while for aniline the binding affinity was decreased and the binding capacity was enhanced. Results indicate specific/selective impairment of the hepatic microsomal cytochrome P450 system during hookworm infection and may have many practical implications in toxicology and pharmacology.

Prednisolone, a potent glucocorticoid, is well known for its immunosuppressive effects on animals. A single dose of 100 microg, 200 microg and 300 microg prednisolone/kg body weight was administered in Swiss albino male mice. Seven days after treatment, the animals were sacrificed to investigate the effect of prednisolone on hepatic and muscular protein contents and glycogen levels along with the level of blood glucose. A catabolic effect on the protein level was evidenced but at the same time the mice became hypoglycemic.

The present report describes the changes in cyclic AMP level which occur upon parasitization of red cells by Plasmodium berghei. Parasitized erythrocytes were separated from the non-parasitized population by percoll density-gradient centrifugation. An increase in the cyclic AMP content of both non-parasitized and parasitized erythrocytes of infected animals compared with that of uninfected animals was observed. The patterns of physiological response to isoproterenol in normal, parasitized and non-parasitized erythrocytes were identical.

The rat prostate is composed of two anatomically well-defined regions designated as the ventral prostate (VP) and the dorsolateral prostate (DLP). VP and DLP are known to exhibit marked cytological, biochemical, and functional differences including differential susceptibilities to carcinogens. While the VP is uniquely susceptible to cadmium carcinogenicity [1,2], the DLP is sensitive to sex hormone-induced cancer [3,4]. The role played by the heavy metal binding protein, metallothionein (MT), in the prostate is largely unknown. It is still controversial as to whether MT is expressed in the rat gland. The aim of the present study is to examine the expression pattern of MT mRNA in the rat gland and its probable regulation by heavy metal ions and sex hormones, in order to gain insight into the biological function of MT in the prostate. Northern hybridization and reverse transcriptase-polymerase chain reaction analyses revealed constitutive expression of MT mRNA in the DLP and a lack of expression of the transcript in the VP. In situ hybridization localized the transcript to the epithelium of the DLP, with the lateral prostate epithelium exhibiting the highest level of expression. Administration of cadmium and zinc failed to induce MT transcription in the VP, nor were these treatments effective in elevating levels of MT mRNA in the DLP. A 60% reduction in MT message levels was observed in the DLP following orchiectomy. MT transcript levels in the DLPs of castrates were restored by readministration of androgen to the animals. Long-term treatments (16 weeks) of rats with estradiol-17 beta (E2) or testosterone (T) plus E2 induced a 2.8-fold and a 5-fold increase in MT message content in the DLP, respectively. In sum, MT mRNA was shown to be absent in the VP and was not inducible by heavy metal ions or hormones in this prostatic lobe. These findings substantiate the belief that MT plays a role in heavy metal detoxification and deficiency in its expression may contribute to the unique susceptibility of the VP to cadmium carcinogenicity. By contrast, constitutive expression of MT was demonstrated in the DLP, which was shown to be regulated by androgen and not by exogenously administered heavy metal ions. These results suggest a participatory role of MT in the normal functioning of the DLP. The fact that high levels of MT mRNA were induced in the DLP following long-term estrogenic or conjoint androgenic-estrogenic action alludes to the possibility that MT may serve as an intracellular antioxidant in DLP cells.

Polyamine levels of some helminth parasites were analyzed by reverse phase HPLC of benzoyl derivatives. Setaria cervi, Acanthocheilonema viteae, Hymenolepis nana, H. diminuta, and Ascaridia galli contained higher levels of spermine than spermidine while in Ancylostoma ceylanicum and Nippostrongylus brasiliensis the spermidine levels were higher than spermine; putrescine was either absent or present in minor quantities. The enzymes of polyamine biosynthesis viz., ornithine decarboxylase, S -adenosyl methionine (SAM)-decarboxylase, and arginine decarboxylase were present in very low to negligible amounts in all the parasites examined. A. ceylanicum exhibited high activity of ornithine amino transferase (OAT) and catalyzed appreciable decarboxylation of ornithine. The ornithine decarboxylating activity of A. ceylanicum was localized in the participate fraction containing mitochondria, not inhibited by α-difluoromethyl ornithine, the specific inhibitor of ornithine decarboxylase (ODC), but inhibited in the presence of glutamate, suggesting the involvement of mitochondrial OAT rather than a true ODC in ornithine decarboxylation in this parasite. Significant activity of polyamine oxidase was also detected in helminth parasites. The absence of polyamine biosynthesizing enzymes in helminth parasites suggests their dependence on hosts for uptake and interconversion of polyamines, providing a potential target for chemotherapy.

S. cervi showed particulate bound Ca2+ ATPase and Na+,K(+)-ATPase activities while Mg2+ ATPase was detected in traces. ATPase of S. cervi was also differentiated from the nonspecific p-nitrophenyl phosphatase activity. Female parasite and microfilariae exhibited higher Ca2+ ATPase and Na+,K(+)-ATPase activities than the male adults and the enzyme Na+,K(+)-ATPase was mainly concentrated in the gastrointestinal tract of the filarial parasite. Na+,K(+)-ATPase of the filariid was ouabain-sensitive while Ca2(+)-ATPase activity was regulated by concentration of Ca2+ ions and inhibited by EGTA. Phenothiazines, viz. trifluoperazine, promethazine and chlorpromazine caused significant inhibition of Ca2+ ATPase and Na+,K(+)-ATPase. Diethylcarbamazine was a potent inhibitor of these ATPases. Mebendazole, levamisole and centperazine also caused significant inhibition of the ATPases indicating this enzyme system as a common target for the action of anthelmintic drugs.

Mebendazole and thiabendazole were found to inhibit glucose uptake and its metabolism in the adult rat hookworm (N. brasiliensis) in vitro. Rates of endogenous glycogen utilisation, and excretion of one of the end products of glycolysis viz., lactic acid, were found to be increased, when the intact N. brasiliensis adults were incubated for 60 min with mebendazole and thiabendazole, respectively.

Ancylostoma ceylanicum infection in golden hamsters (Mesocricetus auratus) caused marked biochemical and histopathological derangements. Jejunum, the primary site of infection, showed pronounced alterations compared with liver. Though the biochemical composition of jejunum was not significantly altered, activities of a few lysosomal enzymes were enhanced during hookworm infection. Marked damage to mitochondrial and microsomal membranes was reflected in changes in the activities of the marker enzymes from jejunal tissue. Lipid content, especially phospholipids and neutral lipids of hepatic tissue, exhibited marked elevation. Levels of hexokinase, phosphofructokinase, and lactate dehydrogenase were enhanced in jejunal as well as hepatic tissues, indicating activation of the glycolytic machinery during hookworm infection. A decrease in the levels of mucosal disaccharidases indicated damage to intestinal brush border membranes. However, alkaline phosphatase activity was increased in intestinal mucosa during the infection. Light microscopic examination of jejunal tissue revealed peeling off of the upper epithelial layer, activation of the goblet cells, and thickening of muscularis mucosa. However, hepatic tissue did not show gross alterations, except for slight necrosis in the centrilobular region.

The protein and antigenic pattern of adult (female/male) and microfilarial stages of Setaria cervi, a bovine filarial parasite, was studied using certain immunochemical techniques. SDS-polyacrylamide gel electrophoretic analysis showed the presence of 35–40 protein bands in adults and 25–29 protein bands in microfilariae in molecular weight range of 10,000–200,000. Immunoelectrophoresis revealed the presence of 9–10 precipitin lines in adult and only 4 precipitin lines in microfilarial antigenic preparations. Crossed immuno-electrophoresis resolved these antigenic preparations further, and revealed the presence of 22–24 antigens in adults and 12–14 in microfilariae. These results demonstrate complex nature of somatic extracts of adult stage as compared to microfilariae and also reveal some qualitative and quantitative differences between these stages.

Tekwani B. L., Tripathi L. M., Mukerjee S., Visen P. K. S., Katiyar J. C., Shukla O. P. and Ghatak S. 1988. Status of the microsomal mixed function oxidase system in the intestine, lungs and kidneys of hamsters during infection with Ancylostoma ceylanicum . International Journal for Parasitology 18 : 11–14. Infection of golden hamsters with Ancylostoma ceylanicum causes significant alterations in microsomal cytochrome P-450 and associated components in intestine, lungs and kidneys. In intestinal microsomes, cytochrome P-450, cytochrome b 5 , heme, cytochrome b 5 reductase, NADPH-cytochrome c reductase and benzo(a)pyrene hydroxylase decreased considerably. This generalized damage in jejunal microsomes appears to be due to marked pathological lesions in this tissue. Lung microsomes exhibited a decrease in cytochrome P-450, heme and benzo(a)pyrene hydroxylase, while cytochrome b 5 , and cytochrome b 5 reductase were not significantly affected. Renal microsomes showed elevation in cytochrome P-450 and benzo(a)pyrene hydroxylase, while other associated components remained unaffected.

SUMMARYGlycogen reserves of whole worms and their body wall, intestines, ovarian and testicular tubules of the avian intestinal nematode,Ascaridia galli, were assayed and on dry-weight basis found to be 14–20 %, except in the testicular tissue which contained only 7 % glycogen.Segments of whole male worms or testicular tubules were found to produce more lactic acid than segments of whole female worms or ovarian tubules. The body wall and intestine of the worms had also appreciable glycolytic activity. Whereas in the segments of whole worms, male and female alike, glycolysis was more active under anaerobic conditions, no differences in glycolytic rates were seen between aerobiosis and anaerobiosis when isolated tissues were used. Exogenously added glucose did not stimulate glycolysis either aerobically or anaerobically to any extent greater than observed in the absence of glucose.Homogenates of whole worms or their different anatomical parts were assayed for enzymic activities associated with the Embden-Meyerhof pathway of glucose assimilation. The crude extracts prior to differential centrifugation, were found to contain glycogen phosphorylase, aldokinases, pyruvate kinase, phosphatases acting on glucose 6-phosphate and hexose diphosphate and 6-phospho-gluconate dehydrogenase. The 105000gparticulate-free supernate was found to have significant activities of the following enzymes: fructokinase, phosphoglucomutase, phosphoglucoseisomerase, phosphofructokinase, aldolase, glyceraldehyde 3-phosphate dehydrogenase, lactic dehydrogenase and glucose-6-phosphate dehydrogenase. This fraction was devoid of NADH or NADPH oxidase activities in the absence of added substrates.Although there was some indication of a negative correlation between low glycogen reserves and high glycolytic activity in the testicular tubules, in general, there was no relationship between glycogen reserve and glycolytic activity on the one hand or between the rate of glycolysis and the specific activities of some of the key glycolytic enzymes in either whole worm or in tissues other than the testicular tubules.The 105000gsupernate was fractionated with ammonium sulphate. The fraction precipitating between 25 and 80 % saturation of the salt was recovered, dialysed and chromatographed on DEAE cellulose column. By a step-wise elution schedule using increasing molarity of NaCl in tris-HCl buffer, pH 7·4, three main protein fractions were obtained representing respectively enolase, aldolase and glucose-6-phosphate dehydrogenase.The recovery of enzyme activity after chromatography on DEAE cellulose was higher than the amount applied to the column suggesting that during the fractionation some naturally occurring inhibitors were removed. About 10- to 20-fold purification of the enzymes was achieved by anion-exchange chromatography.Some properties of the purified enzymes were studied with respect to the affects of enzyme and substrate concentrations, temperature of preincubation and action of divalent cations, some anions, metal chelating agents and SH reagents. The Kmvalues of enolase, aldolase and glucose-6-phosphate dehydrogenase ofA. galliwere 5·9 × 10−4M, 4·5 × 10−3M and 2·4 × 10−3M respectively. Glucose-6-phosphate dehydrogenase was found to be very sensitive to both heat and cold losing activity rapidly even at 43 °C or by freezing and thawing.The SH groups of aldolase were readily blocked bypCMB and presumably byo–phenanthroline. No requirement of any divalent cations was shown by this enzyme which was, however, inhibited by borate ions.Enolase ofA. gallishowed a requirement of Mg2+for full activation. Phosphate, fluoride, EDTA,o–phenanthroline, αα-bipyridyl inhibited the enzyme. Veronal was found to inactivate the enzyme.Glucose-6-phosphate dehydrogenase ofA. galliwas also found to be sensitive to SH reagents and metal chelating agents. The enzyme was activated by Co2+, Mn2+and Mg2+.The evidence presented indicates that segments of whole worms ofA. gallior its anatomical parts are equipped with the enzymatic machinery required to mediate anaerobic breakdown of glucose and to derive energy by this mechanism.The authors are grateful to Dr R. K. Kaushik for help in identifying the worms, to Mr P. A. George for help in the statistical analysis of the data and to Messrs A. C. Kol and S. K. Bose for skilful technical assistance.

The investigation of protein kinase activity in different life stages of a few filarial worms indicates the presence of different protein kinases and of dissimilarities between the distribution pattern of these enzymes during the development. Phosvitin turned out to be the preferred exogenous acceptor protein, when homogenates of adults of Brugia malayi, Dipetalonema viteae, Setaria cervi and Litomosoides carinii were used as source of enzyme. In contrast to adults the L3-larval and the microfilarial stages demonstrated much lower phosvitin phosphorylating activity and the preference for acidic and basic proteins as phosphate acceptors was about equal. The occurrence of cyclic AMP-dependent protein kinase was established for adults of B. malayi.

Ascaris lumbricoides var. hominis and Ascaridia galli contain 5-hydroxytryptamine, histamine, dopamine, and norepinephrine. The chick parasite showed lower levels of monoamines compared to human ascaris. Amine concentrations in females were higher than in males. In all specimens, 5-hydroxytryptamine was the highest while norepinephrine was found to be uniformly low. The female reproductive organ contained the maximum amount of dopamine while intestine was rich in histamine. A progressive increase in the concentrations of biogenic amines was noticed during development.

The pattern of activity of certain membrane-associated enzymes was followed in the erythrocytes of Plasmodium berghei-infected Mastomys natalensis. Parasitized erythrocytes were separated from non-parasitized populations by percoll-density gradient centrifugation. The activity of adenylate cyclase was markedly increased while those of ATPase, acid phosphatase, beta-glucuronidase and N-acetyl-beta-D-glucosaminidase were considerably decreased in the membrane preparations of parasitized erythrocytes as compared to normal erythrocytes. There was a decrease in the activity of ATPase and an increase of adenylate cyclase in the membrane preparations of non-parasitized erythrocytes. However, other enzymes did not alter to a significant extent in non-parasitized erythrocytes. Chloroquine (in vitro) stimulated adenylate cyclase, Na+, K+-ATPase and Ca++Mg++-ATPase while acetylcholinesterase was significantly inhibited.

The status of glycogen, protein, lipid components, lipid peroxides and a few enzymes of energy metabolism was studied in liver of Mastomys natalensis during the development of Brugia malayi infection. Glycogen and lipid contents were decreased during the patent phase of infection while total protein was slightly altered in latent animals. Phospholipid and triglyceride contents declined at prepatent and patent phase of infection. The levels of lactate and malate dehydrogenases, as well as of adenosine triphosphatases (Na+K+, Mg2+, Ca2+), were significantly elevated and monoamine oxidase activity was decreased at patent phase of infection, while succinic dehydrogenase remained unaltered. The lipid peroxide formation was enhanced in liver during the development of filarial infection.

Excretory-secretory products (ES) of Setaria cervi, a bovine filarial parasite, were prepared by in vitro maintenance of the worms in a protein free defined medium at 37 degrees C. RPMI-1640 medium proved to be the best as the worms remained motile in it for the maximum period of time without change of medium, and approximately 12-15 mg protein per 100 adult worms could be obtained. Crossed immunoelectrophoretic analysis of ES products revealed 11-15 antigens and most of them were common to somatic antigenic preparations from both adult worms and microfilariae. The ES products were also found to contain 3-4 host proteins, including serum albumin.

Activities of certain acid hydrolases of the spleen were followed in three different rodents during the course of Plasmodium berghei infection. In albino rats where sterile immunity against the infection develops, the specific activities of a few acid hydrolases first declined then increased from day 7 and showed a several-fold increase over control values when there were no detectable parasites in peripheral circulation. In contrast, in Mastomys natalensis and albino mice which succumb to infection the levels of these enzymes were reduced throughout the course of infection. These results indicate a close correlation between host resistance to infection and the level of lysosomal enzymes in spleen.