RESUMO
Though it is thousands of years old, prostate cancer (PCa) has only been known for 200 years. Until about 50 years ago, the diagnosis could only be made by digital rectal examination. Although the first prostate biopsies were already implemented in the beginning of the last century, it only obtained importance with the introduction of prostate-specific antigen (PSA) testing in the early screening for PCa and the pathologist, thus, became an essential partner for the urologist. In more recent years, specific MRI has significantly increased the accuracy of prostate biopsies. Thus, the question arises whether this technique is going to be so meaningful one day that prostate biopsy and the associated pretherapeutic histology are going to be redundant.
Assuntos
Antígeno Prostático Específico , Neoplasias da Próstata , Biópsia , Exame Retal Digital , Humanos , Masculino , Palpação , Neoplasias da Próstata/diagnósticoRESUMO
BACKGROUND: Physical inactivity is a key contributor to the global burden of disease and disproportionately impacts the wellbeing of people experiencing mental illness. Increases in physical activity are associated with improvements in symptoms of mental illness and reduction in cardiometabolic risk. Reliable and valid clinical tools that assess physical activity would improve evaluation of intervention studies that aim to increase physical activity and reduce sedentary behaviour in people living with mental illness. METHODS: The five-item Simple Physical Activity Questionnaire (SIMPAQ) was developed by a multidisciplinary, international working group as a clinical tool to assess physical activity and sedentary behaviour in people living with mental illness. Patients with a DSM or ICD mental illness diagnoses were recruited and completed the SIMPAQ on two occasions, one week apart. Participants wore an Actigraph accelerometer and completed brief cognitive and clinical assessments. RESULTS: Evidence of SIMPAQ validity was assessed against accelerometer-derived measures of physical activity. Data were obtained from 1010 participants. The SIMPAQ had good test-retest reliability. Correlations for moderate-vigorous physical activity was comparable to studies conducted in general population samples. Evidence of validity for the sedentary behaviour item was poor. An alternative method to calculate sedentary behaviour had stronger evidence of validity. This alternative method is recommended for use in future studies employing the SIMPAQ. CONCLUSIONS: The SIMPAQ is a brief measure of physical activity and sedentary behaviour that can be reliably and validly administered by health professionals.
Assuntos
Exercício Físico , Transtornos Mentais , Comportamento Sedentário , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Inquéritos e Questionários , Adulto JovemRESUMO
The history of kidney transplantation is a history of many unsuccessful efforts and setbacks, but also the history of perseverance, pioneering spirit, and steadfast courage. The first successful transplantation of a dog kidney was done by the Austrian Emerich Ullmann (1861-1937) in 1902. The kidney was connected to the carotid artery of the dog and the ureter ended freely. The organ produced urine for a couple of days before it died. In 1909, there were efforts to transplant human kidneys from deceased patients to monkeys and in the following year the first xenotransplantation in humans was completed. Different kinds of donors were tried: dogs, monkeys, goats and lambs, all without success. In 1939, the first transplantation from a deceased human donor was done by the Russion Yurii Voronoy, the patient survived for only a couple of days, and the organ never worked. In 1953, the first temporarily successful transplantation of a human kidney was performed by Jean Hamburger in Paris. A 16-year-old boy received the kidney of his mother as living donor transplantation. Then in 1954, a milestone was made with the first long-term successful kidney transplantation by Joseph Murray: the transplantation was done between monozygotic twins; the organ survived for 8 years. For his efforts in kidney transplantation, Murray was honored with the Nobel Prize in medicine in 1990. In 1962, the first kidney transplantation between genetically nonrelated patients was done using immunosuppression and in 1963 the first kidney transplantation in Germany was done by Reinhard Nagel and Wilhelm Brosig in Berlin. The aim of this article is to present the history of kidney transplantation from the beginning until today.
Assuntos
Falência Renal Crônica/história , Falência Renal Crônica/terapia , Transplante de Rim/história , Nefrologia/história , Europa (Continente) , História do Século XIX , História do Século XX , História do Século XXI , HumanosRESUMO
Henry II (1519-1559) of France was the second son of Francis I (1494-1547) and Claude de France (1498-1524) born in 1519 in St. Germain-en-Laye. After his older brother's and his father's death in 1547, he was anointed the French king in Reims. In 1533 already, as a 14-year-old boy, for reasons of state, he was married to the same aged Catherine de Medici (1519-1589), as her uncle was Pope Clement VII (1478-1534). The marriage remained childless for 11 years since Henry, due to a distinct hypospadia and a completely sexually inexperienced wife was unable to conceive children with her. His existing liaison to Diane de Poitiers (1499-1566) - a 19-year-older maid of honor of his father Francis I from 1537 until his death - influenced his sexual life immensely.The blame for the childless marriage was placed primarily on his wife, as Henry had become father of an illegitimate daughter with a mistress. Catherine then underwent all possible medical and alchemical procedures to finally give birth to the hoped Dauphin. Ironically, her rival for the favor of her husband, Diane de Poitiers was one of her greatest allies. She made clear that the cause lay with Henry and not with his wife. This was confirmed by the added solid physician Jean Fernel (1497-1558). His treatment of Henry and the simultaneous training of the unexperienced Catherine by Diane de Poitiers led to success.The result was the birth of Francis II (1544-1560) in 1544, the first of 10 children in 12 years. Thus, the dynasty was saved. After the death of Henry in a tragic tournament accident in 1559, three of his sons became kings of France. But the line of Valois remained without further descendants and was continued by Henry IV, the first Bourbon king in 1589.
Assuntos
Pessoas Famosas , Hipospadia/história , Infertilidade Masculina/história , Urologia/história , França , História do Século XVI , Humanos , MasculinoRESUMO
BACKGROUND: In 2011 the WPATH (World Professional Association for Transgender Health) published the 7th version of their "Standards of Care" for diagnosis and treatment of transsexual people. In face of further recent peer-reviewed reports of experienced centres on surgical sex reassignment it should be examined whether or not genital sex reassignment in male-to-female transsexuals actually can be based on evidence-based guidelines or standards. RESULTS: The indication for surgery is widely standardised and evidence-based. Most critical steps of the operation are also founded on grade B recommendations. Most experienced authors rely on penoscrotal pedicled flaps for neovaginal lining. The topic of ideal reconstruction of the vulva, especially the clitoro-labial complex is still a field of debate. Due to the high frequency of further corrective surgeries which exceeds 50% in most experienced centres, some authors prefer a primary 2-step procedure for genital reassignment. CONCLUSIONS: The indication and principal operative steps in surgical genital reassignment in male-to-female patients rely on evidence-based recommendations. By respecting these recommendations subjective success rates of over 80% can be expected.
Assuntos
Guias de Prática Clínica como Assunto , Cirurgia de Readequação Sexual/normas , Transexualidade/cirurgia , Comportamento Cooperativo , Medicina Baseada em Evidências/normas , Humanos , Comunicação Interdisciplinar , Satisfação do Paciente , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Reoperação , Fatores de Risco , Retalhos Cirúrgicos/cirurgiaRESUMO
Dimitri Oscarovic Ott (1855-1929) can be justified in calling himself one of the true pioneers of laparoscopy and especially of natural orifices transluminal endoscopic surgery (NOTES). As early as 1901 he performed abdominal examinations via a transvaginal access and called this procedure ventroscopy. The publication of his first results and a description of the method and equipment were released in 1902. He was one of the pioneers of present day laparoscopy in addition to Georg Kelling (1866-1945) and Hans Christian Jacobaeus (1879-1937).While Kelling published and presented his first results of animal trials in 1901 and 9 years later in 1910 Jacobaeus performed his first interventions on human beings, Ott had already used the new method developed by him in clinical practice since 1901. Through a single incision in the cul-de-sac and using a head lamp system similar to reflector lamps used by otolaryngologists, he inspected the abdominal cavity with the aid of a gynecological speculum. The patient was positioned in an extreme head-down position and for better lighting he used an additional light source which was connected to the speculum. Even today Prof. Ott is a legend in Russia and especially in St. Petersburg. He was director of the National Institute of Obstetrics and personal physician to Tsarina Aleksandra Fedorovna (1874-1918). He is regarded as the father of the Russian school of obstetrics and gynecology as well as founder of endoscopic surgery and laparoscopy in Russia.
Assuntos
Endoscopia/história , Ginecologia/história , Laparoscopia/história , Obstetrícia/história , História do Século XIX , História do Século XX , Federação RussaRESUMO
Dominique-Jean Larrey (1766-1842) was Surgeon-in-Chief of the Grande Army under Napoleon Bonaparte (1769-1821) and personal physician of the Emperor. Against the opposition of the traditionalists he introduced the "ambulances volantes", the so-called flying ambulances. The aim was the medical treatment of the injured soldiers immediately on the battlefield. This revolutionary treatment led to a benefit not only for the own soldiers, but also for the wounded enemies. His innovation in the field of immediate assistance of wounded persons, together with Larreys' outstanding medical competence, saved thousands of soldiers lives on the battlefield of the Napoleonic wars. His memories concerning the military campaigns, have been even up to the 20th century one of the standard works of modern military surgery. He had as well great interest in urolological injuries of the urinary system and their conservative and operative care. Up to these days, his work shows a surprising actuality and perfect anatomic understanding. In a time without anaesthetics, antibiotics and under primitive circumstances, Larrey and his collegues accomplished surgical feats. Larreys flying ambulances were copied by many different countries. The American Mobile Army Surgical Hospital (M.A.S.H) is clearly based on his thoughts and ideals. In our opinion he is the father of the modern war surgery as well the urological traumatology.
Assuntos
Medicina Militar/história , Traumatologia/história , Urologia/história , França , História do Século XVIII , História do Século XIXRESUMO
For hardly any other organ can the development of medicine and technical advances in the last 150 years be so clearly illustrated as for the prostate. The history of radical prostatectomy was initially characterised by the problems in approaching this relatively difficulty accessible organ. In 1867, Theodor Billroth in Vienna performed the first partial prostatectomy via a perineal access. In 1904, Hugh Hampton Young and William Stewart Halsted at the Johns Hopkins Hospital in Baltimore / USA carried out the first successful extracapsular perineal prostatectomy and opened up a new era. In Germany, Prof. Friedrich Voelcker in Halle in 1924 developed the so-called ischiorectal prostatectomy. But it was left to Terence Millin to publish in 1945 the first series of retropubic prostatectomies. In 1952, the sacroperineal approach according to Thiermann and the sacral prostatectomy according to were introduced. Finally, in 1991 another new era in prostate surgery started with the first laparoscopic prostatectomy. This development peaked in 2011 with the presentation of the laparoscopic DaVinci prostatectomy by Binder. Originally a stepchild of urological surgery that was to be avoided whenever possible due to the fear of serious complications, the prostate has progressed in the course of time to an obscure object of lust. The stepchild has become the favorite child.
Assuntos
Laparoscopia/história , Prostatectomia/história , Neoplasias da Próstata/história , Robótica/história , Europa (Continente) , História do Século XIX , História do Século XX , História do Século XXI , Humanos , Masculino , Estados UnidosRESUMO
For many societies in the world onanism is taboo because of religious and medical ethics. From ancient times until the present day this type of body sensation is disclaimed by modern communities like a recurrent theme. After the discovery of the mechanism of fertilisation by the biologist Eduard van Beneden (1846-1910) in 1875 the feminine clitoris was declared to be a dispensable organ. The clitoris was suspected of causing hysteria, epilepsy and other forms of insanity. In the eighteenth century masturbation performed by young men was classified as a consumptive disease that caused inevitable death. The following presentation gives an historical overview through the history of onanism that demonstrates the artistic, philosophical and medical point of view on the sexuality of men.
Assuntos
Coito Interrompido , Anticoncepção/história , Urologia/história , História do Século XVII , História do Século XVIII , História do Século XIX , História do Século XX , HumanosRESUMO
A 46-year-old man presented with severe pain in our emergency department. In addition he had macrohematuria, the further medical history was inconspicuous. The pain showed to be resistant to therapy, therefore we performed a CT scan of the abdomen. The CT scan showed a partial embolism of the right renal artery, a thrombus of the aorta thoracica as well as partial infarction of the spleen and the liver. An immediately initiated therapy with implantation of an aortal stent graft for fixation of the thrombus and an Actilyse® therapy led to full recovery of the patient. Closer questioning of the patient showed that the patient undertook an extended abdominal and thoracic muscle training programme by letting an eight-kilogram bowling ball fall down onto his abdomen from about 80 cm height. The diagnosis embolism of the renal artery cannot be made without extended diagnostics in the emergency room. A good hint for perfusion disorders of the kidney can be obtained with duplex ultrasound. Therapy-resistant pain without hydronephrosis and concomitant arrhythmia of the patient can lead to the diagnosis. The initiation of an adequate diagnosis and therapy is essential as otherwise persisting perfusion disorders of the kidney may occur.
Assuntos
Traumatismos Abdominais/complicações , Traumatismos Abdominais/etiologia , Aorta Torácica/lesões , Doenças da Aorta/etiologia , Traumatismos em Atletas/complicações , Traumatismos em Atletas/etiologia , Embolia/etiologia , Obstrução da Artéria Renal/etiologia , Artéria Renal/lesões , Treinamento Resistido , Trombose/etiologia , Ferimentos não Penetrantes/complicações , Ferimentos não Penetrantes/etiologia , Traumatismos Abdominais/terapia , Doenças da Aorta/terapia , Traumatismos em Atletas/terapia , Embolia/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Obstrução da Artéria Renal/terapia , Stents , Terapia Trombolítica , Trombose/terapia , Ativador de Plasminogênio Tecidual/uso terapêuticoRESUMO
Innovative techniques have a really magical attraction for physicians as well as for patients. The number of robotic-assisted procedures worldwide has almost tripled from 80,000 procedures in the year 2007 to 205,000 procedures in 2010. In the same time the total number of Da Vinci surgery systems sold climbed from 800 to 1,400. Advantages, such as three-dimensional visualization, a tremor-filter, an excellent instrument handling with 6 degrees of freedom and better ergonomics, together with aggressive marketing led to a veritable flood of new Da Vinci acquisitions in the whole world. Many just took the opportunity to introduce a new instrument to save a long learning curve and start immediately in the surgical master class.If Da Vinci sacrocolpopexy is compared with the conventional laparoscopic approach, robotic-assisted sacrocolpopexy shows a significantly longer duration of the procedure, a higher need for postoperative analgesics, much higher costs and an identical functional outcome without any advantage over the conventional laparoscopic approach. Although the use of robotic-assisted systems shows a significantly lower learning curve for laparoscopic beginners, it only shows minimal advantages for the experienced laparoscopic surgeon. Therefore it remains uncertain whether robotic-assisted surgery shows a significant advantage compared to the conventional laparoscopic surgery, especially with small reconstructive laparoscopic procedures such as sacrocolpopexy.
Assuntos
Procedimentos Cirúrgicos em Ginecologia , Procedimentos Cirúrgicos Minimamente Invasivos , Diafragma da Pelve/cirurgia , Robótica , Cirurgia Assistida por Computador , Feminino , Humanos , Laparoscopia , Procedimentos de Cirurgia PlásticaRESUMO
A 29-year-old depressed, otherwise healthy female patient was treated with agomelatine and duloxetine. She developed subsequent akathisia, which subsided after cessation of agomelatine. As a cause we suggest a pharmacodynamic drug-drug interaction leading to noradrenergic overstimulation. We recommend only gradual dose titration when combining the 2 substances to minimize the risk for side effects.
Assuntos
Acetamidas/efeitos adversos , Acatisia Induzida por Medicamentos/etiologia , Antidepressivos/efeitos adversos , Hipnóticos e Sedativos/efeitos adversos , Tiofenos/efeitos adversos , Adulto , Transtorno Depressivo Maior/tratamento farmacológico , Cloridrato de Duloxetina , Feminino , HumanosRESUMO
Professor Dr. Anton Ritter von Frisch was born in Vienna on 16 February 1849 where he was appointed Head of the Special Department for Diseases of the Urinary Organs at the General Polyclinic in 1889. Numerous publications and textbooks on urology can be attributed to him. From a historical perspective, he is particularly distinguished by the fact that he was elected as the first President of the German Society of Urology in 1907 in Vienna and was even designated to become President for a second time for the 1915 Congress, which however was never organized due to the outbreak of World War I. His early death in 1917 at the age of only 68 brought an end to his exceptionally productive and successful efforts on the part of urology.
Assuntos
Liderança , Sociedades Médicas/história , Urologia/história , Áustria , Alemanha , História do Século XIX , História do Século XXRESUMO
Apparently unimportant diseases of some prominent figures can have a considerable effect on the course of time at turning points in world history. It is quite conceivable that the Battle of Waterloo on 18 June 1815 had been lost by France because Napoleon was not in full possession of his powers, because he was suffering from acute cystitis. Adverse weather conditions with continuous rain and coldness in advance of the battle, extremely primitive hygienic conditions and more than simple quarters for the night led to the development of cystitis. Based on the records of his biographers, his personal physician and the letters to his brother, we know that Napoleon was not able to give the command to attack in the early morning as intended, but in the early noon, only because of his bad general condition. This delay of several hours led, as we all know, to the intervention of Prussia and the devastating defeat of France. Thus it appears that a relatively unimportant urological disease influenced the course of world history crucially.
Assuntos
Cistite/história , Pessoas Famosas , Guerra , França , História do Século XIX , Humanos , MasculinoRESUMO
INTRODUCTION: In literature cystic tumours and carcinomas of the urachus are commonly described, also the secondary infection of a urachal cyst leading to an abscess is not unusual. But a foreign body penetrating after spontaneous perforation into an existing bland urachal cyst leading to an abscess is extremely rare and not described in literature. Although we made a thorough and extensive literature search we were not able to find a similar case. CASE REPORT: This report concerns a 38-year-old female patient suffering from diffuse pain in the lower abdomen as well as temperatures up to 39 degrees C referred for further diagnostics and treatment. Further examinations showed an infra-umbilical 6 x 6 cm cystic formation. A CT scan confirmed our suspicion of an inflammatory cystic finding in this area. A subsequent laparoscopic transabdominal excision of this region was -performed. The histological analysis showed a central abscess-forming urachal cyst. Centrally located and causal for the inflammatory process we found a 4-cm fishbone. Even after closer question-ing there was no anamnestic evidence of how this foreign body could have got there. A self-manipulation was resolutely and believably denied by the patient. CONCLUSION: In our opinion this case is an absolute rarity due to the constellation of two extremely seldom components: a urachal cyst and a probable intestinal perforated foreign body.
Assuntos
Abscesso Abdominal/diagnóstico , Corpos Estranhos/diagnóstico , Cisto do Úraco/diagnóstico , Úraco , Abscesso Abdominal/cirurgia , Adulto , Calcinose/diagnóstico , Calcinose/cirurgia , Diagnóstico Diferencial , Feminino , Corpos Estranhos/cirurgia , Humanos , Laparoscopia , Dor Pélvica/etiologia , Tomografia Computadorizada por Raios X , Ultrassonografia , Cisto do Úraco/cirurgiaRESUMO
OBJECTIVE: Sleep deprivation (SD) can induce a prompt decrease in depressive symptoms within 24h. Following the recovery night, however, a relapse into depression occurs in most patients. Recovery sleep, naps and even very short episodes of sleep (microsleep; MS) during SD have been shown to provoke a rapid relapse into depression. This study tested the hypothesis that modafinil reduces MS during SD and stabilizes the treatment response to PSD compared to placebo. METHODS: A total of 28 patients (13 men, 15 women; age 45.1+/-12.1 years) with a major depressive episode and a cumulative daytime microsleep of five or more minutes were investigated using a double-blind placebo-controlled study design. All patients were treated with a stable mirtazapine monotherapy. A partial SD (PSD) was performed after one week. Additional morning treatment with modafinil vs. placebo started during PSD and was maintained over two weeks. Sleep-EEG and MS episodes were recorded with a portable EEG. Depression severity was assessed using the Hamilton Depression Rating Scale before, during and after PSD and at follow-ups after one and two weeks. RESULTS: Patients treated with modafinil showed significantly reduced microsleep during PSD (11.63+/-15.99 min) compared to the placebo group (47.77+/-65.31 min). This suppression of MS was not associated with the antidepressive effect of PSD. CONCLUSIONS: Compared to placebo, modafinil was efficient in reducing daytime microsleep following partial sleep deprivation but did not enhance the antidepressive effects of PSD and did not stabilize antidepressive effects over two weeks.
Assuntos
Compostos Benzidrílicos/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Transtorno Depressivo Maior/psicologia , Transtorno Depressivo Maior/terapia , Privação do Sono/fisiopatologia , Fases do Sono/efeitos dos fármacos , Vigília/efeitos dos fármacos , Adulto , Compostos Benzidrílicos/uso terapêutico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Método Duplo-Cego , Eletroencefalografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modafinila , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Índice de Gravidade de DoençaRESUMO
The phenomenon of castration is wedded to the baroque era. This epoch stands for pure sensual pleasure. Those who could afford it tried to arrange their earthly days to be as enjoyable as possible. A perverse bloom of this ambition was the angel-like voices of the castrati. The supernatural sound of the voice was meant to let the opera visitors escape into another world. High society was almost addicted to those voices. On the other hand nobody showed any interest in the spiritual life of the castrati. Farinelli, Nicolini, and Senesino, three of the most famous castrati, were the first musical superstars of the eighteenth century. Their voices moved the decadent baroque audience to tears and enraptured them to the point of standing ovations. But the price for this fame was high. Only through castration in their early boyhood could this bell-like voice be kept. Because of the sensational success of the castrati, a huge wave of castration swept over Italy. Ambitious parents had their boys castrated, hoping that they would also become famous opera stars. It is estimated that in Italy alone over half a million boys were victims of this mutilating procedure during the eighteenth century. Because castration was officially forbidden it was done"behind closed doors" by untrained barbers and of course was associated with a high morbidity and mortality rate. The height of the castrati ended with the fading eighteenth century. The last castrato, Alessandro Moreschi, was engaged as a chorister and soloist at the Sistine Chapel in the Vatican. He was pensioned off by Pope Pius X in the year 1912 after an official ban on castrated singers was imposed. With that a very impressive part of music history had ended.
Assuntos
Castração/história , Abuso Sexual na Infância/história , Música/história , Criança , Pré-Escolar , História do Século XVIII , Humanos , Itália , MasculinoRESUMO
Giacomo Girolamo Casanova was born in Venice, the son of actors, on 2 April 1725. After studying theology and law, he was ordained as an abbé, but after 3 years he left the clergy. In 1742 he graduated with a degree in law but never seriously practiced as an attorney. Occupational episodes included stints as a soldier, secret agent, lottery operator, embassy secretary, and violinist. He became world famous after his escape from "The Leads" (a famous Venetian prison), which he described in detail in his 15-volume, French-language memoirs. Because of his countless romantic adventures, which he also described in great detail, we want to generate a kind of "vita sexualis."His not-so-insignificant medical knowledge, together with his unruly libido as well as his pronounced imagination, led to a more than astonishing career. His experiences and descriptions appear today to be very relevant and testify a great deal about medical laymen's knowledge and ingenuity. For Casanova, the use of different aphrodisiacs or love amulets served only one purpose, and that was to continuously broaden his frivolous adventures.When he died as a result of chronic bladder disease on 4 June 1798 in Bohemia, he left behind - besides the broken hearts of countless women - a fascinating biography that provides a comprehensive and intriguing portrait of the customs of the 18th century.
Assuntos
Afrodisíacos/história , História do Século XVIII , ItáliaRESUMO
We report about a rare case of malakoplakia in a female urethral diverticulum. A 25-year-old patient with a long history of recurrent urinary tract infections and a plum-sized, painful swelling on the vaginal roof presented for operative treatment. In the anamnesis the patient reported about two spontaneous perforations, emptying several millilitres of pus each time. After total operative excision using a vaginal approach the histology showed malakoplakia in a urethral diverticulum. We found the typical intracytoplasmatic "Michaelis-Gutmann bodies" as well as "von Hansemann cells". Postoperatively we excluded an underlying tumour disease or a chronic infection. The further urological diagnostics (cystoscopy and MRI) were without any pathological findings. In patients with atypical cystic tumours of the urogenital tract, especially with an immune deficiency, malakoplakia should be taken in consideration. The preferred therapy is surgical management followed by long-term antibiosis as well as a close follow-up as recurrences are frequent.