An adrenal incidentaloma that had appeared to produce dehydroepiandrosterone-sulfate in excess before immunohistochemical study of the tumor.

Adrenal incidentaloma is a clinically unapparent adrenal mass more than one cm in diameter detected during imaging performed not for adrenal disease. A 34-year-old man was evaluated for AI with a diameter of 3.5 cm in the left adrenal. He was obese with body mass index of 33,9. Blood pressure was 110-120/90 mmHg. The general laboratory tests were unremarkable. An adrenal hormone screening set revealed that ACTH was 6.9 pg/mL, cortisol 14.9 µg/dL, renin activity 0.9 ng/mL/h, aldosterone 79.4 pg/mL, dehydroepiandrosterone-sulfate (DHEA-S) measured on two occasions 5,217 ng/mL and 6,477 ng/mL (gender- and age-adjusted reference values, 1,060-4,640 ng/mL). The levels of metanephrine and normetanephrine were normal. The tumor was thought to produce solely DHEA-S. The excised left adrenal tissue contained a tumor with a diameter of 26 mm and neighboring adrenal tissue. The tumor consisted mostly of acidophil cells without necrosis, capsular or vascular invasion, and mitosis. Immunohistochemical study revealed followings: the cells of the tumors were stained positive for 3ß-hydroxysteroid dehydrogenase, and 17α-hydroxylase, and 11ß-hydroxylase, weakly positive for DHEA sulphotransferase, and negative for aldosterone synthetase. The atrophy of neighboring tissue was presumably caused by excess cortisol production. Four months after surgery, the cortisol level was 11.2 µg/dL and DHEA-S level 1,462 ng/mL. The tumor is considered to be a cortisol-producing adenoma with modestly excessive DHEA-S production rather than isolated DHEA-S-producing adenoma. Immunohistochemical study of steroidogenic enzymes is a valuable addition to blood hormone measurement to clarify steroid production profile.

Lysophosphatidic acid stimulates rat uterine contraction in vitro.

Lysophosphatidic acid (LPA) has been implicated in the uterine endometrial functions of implantation and decidualization; however, not much is known about its myometrial contractile function. Herein we characterized the uterotonic effects of LPA in non-pregnant (estrus) and peri-parturient rats in vitro. LPA dose-dependently (0.01-10 µM) stimulated the amplitude and integral, but not the frequency, of the uterine strip contraction of estrous rats. The stimulatory effect of LPA was enhanced 1 day before parturition but was lost 1 day postpartum. LPA did not cause the de novo synthesis of prostaglandin (PG) F2α but stimulated contractions cooperatively with the PG. LPA-induced contractions were significantly inhibited by an LPA1/2/3 antagonist in the uteri of estrous rats but not in term rats. This study characterized the uterotonic effect of a natural LPA that occurs at physiological concentrations, changes with reproductive states, and is independent of mediation by the newly synthesized PG.

Factors Encouraging Internal Medicine Specialists in Japan to Move towards Certification as General Practitioners.

In Japan, a new medical specialist system started in 2018 and has established the "Comprehensive Medical Specialist" program. The Japan Medical Agency allows specially-appointed supervisors, such as specialists in particular branches of internal medicine, to transfer to the "general practitioner" program. These specialists are often considered as reserve general practitioners. In April 2016, we conducted a survey of 2,666 randomly selected specialists in 11 societies related to the Japanese Society of Internal Medicine. Of the 404 who responded (15.2% response rate), 142 (35.1%) were "certification-oriented." Logistic regression analysis with the outcome of desire for certification as a general practitioner (yes = 1) showed odds of 2.293 (95% confidence interval: 1.379-3.811) for "cannot take the necessary time to prepare" and 12.417 (95% confidence interval: 2.856-53.986) for "should be eligible to take the exam without leaving my current job." Creating an environment that allows specialists in internal medicine across various specialties to prepare for certification as a general practitioner, while continuing to work in their current positions, would help to increase the number of high-quality general practitioners to supply the need in Japan.

Point Prevalence Surveys of Antimicrobial Prescribing in a Non-Acute Care Hospital in Saitama Prefecture, Japan.

Background: The global point prevalence survey (Global-PPS) is the standard for the surveillance of prescribed antimicrobials among inpatients and provides data for the development of hospital antimicrobial stewardship programs. Aim: To evaluate the prevalence and quality of antimicrobial prescriptions using the universally standardized Global-PPS protocol in a non-acute care hospital in Saitama Prefecture, Japan. Methods: Antimicrobial prescriptions for inpatients, staying at the hospital overnight, were surveyed on three separate week days in November 2018, January 2019, and May 2019. Information on the prescribed antimicrobials on the survey target day was obtained from the in-hospital pharmacy. Survey data were collected by physicians, based on the extracted information. Patient information was anonymized and entered in the Global-PPS Web application by physicians. We report the antimicrobial use prevalence, the indication for prescription, diagnosis, the most prescribed antimicrobials, and a set of quality indicators related to antimicrobial prescribing. Results: In total, 6.7% of the surveyed inpatients (120/1796) were prescribed antimicrobials on the survey day. Sulfamethoxazole/trimethoprim was the most commonly prescribed, with 20.0% of systemic antibiotic prescriptions (ATC J01). Of all antibiotics for systemic use, up to 58.4% were Watch antibiotics, as defined by the World Health Organization AWaRe classification. The most prescribed group of systemic antibiotics was non-penicillin beta-lactam antibiotics (34.4%), followed by penicillin antibiotics in combination with beta-lactamase inhibitors (25.6%), and sulfonamides with trimethoprim (20.8%). Healthcare-associated infections and medical prophylaxis were the most common indications reported in 69.3% and 26.3% of prescriptions, respectively. The most common diagnosis for systemic antibiotic prescriptions was pneumonia (49.6%). Reasons for antimicrobial prescriptions were indicated in the medical records for 67.1% of prescriptions, and the stop/review date was documented to be 50.3%. Compliance with local guidelines reached 66.7%. Conclusions: This study highlights important challenges related to antimicrobial prescription in a highly specific, non-acute care patient population.

Phylogeographic and demographic modeling analyses of the multiple origins of the rheophytic goldenrod Solidago yokusaiana Makino.

Understanding adaptation mechanisms is important in evolutionary biology. Parallel adaptation provides good opportunities to investigate adaptive evolution. To confirm parallel adaptation, it is effective to examine whether the phenotypic similarity has one or multiple origins and to use demographic modeling to consider the gene flow between ecotypes. Solidago yokusaiana is a rheophyte endemic to the Japanese Archipelago that diverged from Solidago virgaurea. This study examined the parallel origins of S. yokusaiana by distinguishing between multiple and single origins and subsequent gene flow. The haplotypes of noncoding chloroplast DNA and genotypes at 14 nuclear simple sequence repeat (nSSR) loci and single-nucleotide polymorphisms (SNPs) revealed by double-digest restriction-associated DNA sequencing (ddRADseq) were used for phylogeographic analysis; the SNPs were also used to model population demographics. Some chloroplast haplotypes were common to S. yokusaiana and its ancestor S. virgaurea. Also, the population genetic structures revealed by nSSR and SNPs did not correspond to the taxonomic species. The demographic modeling supported the multiple origins of S. yokusaiana in at least four districts and rejected a single origin with ongoing gene flow between the two species, implying that S. yokusaiana independently and repeatedly adapted to frequently flooding riversides.

The Kiddie Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version (K-SADS-PL) for DSM-5: A validation for neurodevelopmental disorders in Japanese outpatients.

OBJECTIVE: The Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version (K-SADS-PL) is a widely used semi-structured diagnostic interview in child and adolescent psychiatry. However, given the extensive use of the K-SADS-PL in clinical practice and research and its adaptation for use in many languages and cultures, validation studies of the instrument are scarce. This study was designed to examine the inter-rater reliability, criterion validity and construct validity of the updated instrument, the K-SADS-PL for DSM-5, in Japanese outpatients totaling 95 children and adolescents. METHOD: We translated and adapted the updated instrument into Japanese using a standard forward-backward translation procedure. Two of nine experienced clinicians independently made diagnoses using the interview for each patient in a conjoint session. Discrepancies in diagnosis between two clinicians were resolved by consensus, and the consensus diagnosis was compared with a "best-estimate" diagnosis made by five experienced clinicians using all available data sources for patients who were blinded to the diagnosis using the K-SADS-PL for DSM-5. The "best-estimate" diagnosis of ASD was also based on the Diagnostic Interview for Social and Communication Disorders. RESULTS: The inter-rater reliability was very good, as shown by κ ≥ 0.8 for all disorders examined: autism spectrum disorder (ASD), attention-deficit hyperactivity disorder, tic disorders, selective mutism, enuresis and encopresis. The criterion validity was good, as shown by κ ≥ 0.6 for all disorders examined, except for ASD (κ = 0.59). This study also revealed good construct validity of the instrument by confirming the expected associations with each scale from the Social Responsiveness Scale-2nd edition and the Strengths and Difficulties Questionnaire. CONCLUSION: These results suggest that the K-SADS-PL for DSM-5 generates valid diagnoses in child and adolescent psychiatry.

Phylogeographic analysis of the East Asian goldenrod (Solidago virgaurea complex, Asteraceae) reveals hidden ecological diversification with recurrent formation of ecotypes.

Background and Aims: The processes and mechanisms underlying lineage diversification are major topics in evolutionary biology. Eurasian goldenrod species of the Solidago virgaurea complex show remarkable morphological and ecological diversity in the Japanese Archipelago, with ecotypic taxa well adapted to specific environments (climate, edaphic conditions and disturbance regimes). The species complex is a suitable model to investigate the evolutionary processes of actively speciating plant groups, due to its ability to evolve in relation to environmental adaptation and its historical population dynamics. Methods: Two chloroplast markers, 18 nuclear microsatellite markers and ddRAD-sequencing were used to infer population genetic demography of S. virgaurea complex with its related species/genera. Key Results: Our analysis showed that populations in Japan form an evolutionary unit, which was genetically diverged from adjacent continental populations. The phylogenetic structure within the archipelago strongly corresponds to the geography, but interestingly there is no concordance between genetic structure and ecotypic boundaries; neighbouring populations of distinct ecotypes share a genetic background. Conclusions: We propose that the traits specific to the ecotypic entities are maintained by natural selection or are very recently generated and have little effect on the genomes, making genome-wide genetic markers unsuitable for detecting ecotypic differentiation. Furthermore, some sporadically distributed taxa (found as rheophytes and alpine plants) were repeatedly generated from a more widespread taxon in geographically distant areas by means of selection. Overall, this study showed that the goldenrod complex has a high ability to evolve, enabling rapid ecological diversification over a recent timeframe.

Cooperation between Single-Handed and Group Practices Ensures the Replacement of Gastrostomy Tubes and Tracheal Cannulas in Home Medical Care Settings.

In Japan, patients who require home medical care are increasing especially in the elderly. In home medical care settings, devices such as gastrostomy tubes, tracheal cannulas, and urethral catheters are usually replaced by visiting physicians or nurses. However, device replacement services are not always available in Japan. Unless device replacement services are sufficiently provided to patients at home, patients have to suffer various disadvantages, including a forced visit to a hospital for device replacement despite inability to walk. We therefore investigated background factors of clinics and nursing stations providing home-care visits using a cross-sectional postal survey from August to September 2013. We targeted physicians from 5,828 clinics providing home medical care and nurses from 1,798 home-visit nursing stations across six prefectures (Tokyo, Kanagawa, Saitama, Chiba, Miyagi and Iwate). Responses were received from 933 clinics (16.5%) and 552 stations (31.3%). We analyzed the responses using multivariable logistic regression with two models. "Model 1" mainly included the number of full-time staff and the availability of a 24-hour care service system, and "Model 2" mainly included the number of clinics, the number of home-visit nursing stations, and the ratio of the population aged ≥ 65 years to study the influence of medical resources. We thus found that clinic staff numbers and 24-hour care availability were associated with physicians' replacement of gastrostomy tubes and tracheal cannulas (p < 0.001 for each). In conclusion, single-handed and group practices need to cooperate to ensure the replacement of these devices in home medical care settings.

Doctor-patient communication without family is most frequently practiced in patients with malignant tumors in home medical care settings.

Promotion of home medical care is absolutely necessary in Japan where is a rapidly aging society. In home medical care settings, triadic communications among the doctor, patient and the family are common. And "communications just between the doctor and the patient without the family" (doctor-patient communication without family, "DPC without family") is considered important for the patient to frankly communicate with the doctor without consideration for the family. However, the circumstances associated with DPC without family are unclear. Therefore, to identify the factors of the occurrence of DPC without family, we conducted a cross-sectional mail-in survey targeting 271 families of Japanese patients who had previously received home medical care. Among 227 respondents (83.8%), we eventually analyzed data from 143, excluding families of patients with severe hearing or cognitive impairment and severe verbal communication dysfunction. DPC without family occurred in 26.6% (n = 38) of the families analyzed. A multivariable logistic regression analysis was performed using a model including Primary disease, Daily activity, Duration of home medical care, Interval between doctor visits, Duration of doctor's stay, Existence of another room, and Spouse as primary caregiver. As a result, DPC without family was significantly associated with malignant tumor as primary disease (OR, 3.165; 95% CI, 1.180-8.486; P = 0.022). In conclusion, the visiting doctors should bear in mind that the background factor of the occurrence of DPC without family is patient's malignant tumors.

Relationship between the characteristics of Japanese physicians involved in medical care for older adults and their approaches to treating older patients with multimorbidity.

One countermeasure against the increasing prevalence of multimorbidity is the need to provide clinical education and training that considers the characteristics of physicians. We conducted a questionnaire survey to determine the relationship between physicians' characteristics and their approach to treating older patients with multimorbidity. A total of 3300 geriatric specialists and primary care specialists in Japan were enrolled. A 4-point Likert scale was used to score the following items: difficult diseases (43 items), difficult patient backgrounds (14 items), important clinical factors (32 items), and important clinical management (32 items). Exploratory factor analysis was performed to examine the constructs in each of the scales Diseases, Backgrounds, Clinical Factors, and Clinical Management, and group comparisons by physician characteristics were conducted. A total of 778 respondents were included in the analysis. Six factors for Diseases, two factors for Patient Background, four factors for Clinical Factors, and two factors for Clinical Management were explored as patterns. Group comparison between mean scores for each factor and the characteristics of responding physicians showed statistically significant differences in at least one factor for all patterns in terms of years of experience as a physician (26 years or less, 27 years or more), the clinical setting (providing or not providing home medical care), and sex (male or female). Our results suggest a need for clinical education and training that takes into account not only physicians' experience and clinical setting, but also their sex.

Communication between physicians, patients, their companions and other healthcare professionals in home medical care in Japan.

OBJECTIVE: To examine communication in home medical care. METHODS: Conversations that happened during home medical care involving physicians at nine clinics were recorded and analyzed using the Roter Interaction Analysis System (RIAS). Additional categories were developed to code aspects of home medical care. RESULTS: Overall, 55 conversations were analyzed. The mean age of the patients was 82.9 ± 10.1 years old. The most common triad was physician, patient, and patient's companion. Information about home medical care professionals who were not present during the conversation was provided by the physician in 21 cases (38.2%), the patient in nine cases (16.4%), and companions in 21 (39.6%) cases. CONCLUSION: In home medical care, the participants mentioned home medical care professions who were not present at the time, suggesting that these conversations may have facilitated interprofessional collaboration. PRACTICE IMPLICATIONS: Physicians should be aware that during home medical care, the presence of multiple attendants and other medical professionals contributing to communicate with the patient.

Psychometrics of rating scales for externalizing disorders in Japanese outpatients: The ADHD-Rating Scale-5 and the Disruptive Behavior Disorders Rating Scale.

OBJECTIVES: This study validated the Japanese version of the Attention-Deficit/Hyperactivity Disorder-Rating Scale-5 (ADHD-RS-5) and the Disruptive Behavior Disorders Rating Scale. We extended the ADHD-RS-5 by adding the oppositional defiant disorder and conduct disorder subscales to compare the two rating scales psychometrically. METHODS: We examined the internal consistency, test-retest reliability, construct validity and criterion validity of the two rating scales in 135 Japanese outpatients aged 6-18 years. RESULTS: The internal consistency and test-retest reliability were good for all the subscales of the two rating scales except for the conduct disorder subscale of the ADHD-RS-5 extended. Good construct validity was revealed by expected correlational patterns between subscales from the two rating scales and the Children Behavior Checklist. The criterion validity was good for all the subscales of the two rating scales rated by parents, while teacher-ratings revealed substantially lower predictive ability for all the subscales. Agreement between parent- and teacher-ratings of the two rating scales was generally moderate and using predictive ratings alone of both ratings showed the best predictive ability among the integration methods examined. CONCLUSION: The two rating scales have sound psychometric properties and will aid in screening and severity assessment of externalizing disorders in Japanese clinical settings.

Questionnaire survey of geriatricians and primary care physicians' approaches to treating older patients with multimorbidity.

AIM: Geriatricians and primary care physicians in Japan are expected to provide care to older patients with multimorbidity. METHODS: A questionnaire survey was carried out to understand the current approaches to older patients with multimorbidity. A total of 3300 participants, including 1650 geriatric specialists (G) and 1650 primary care specialists (PC) were enrolled. A 4-point Likert scale was used to score the following items: diseases that cause difficulty in treatment (diseases), patient backgrounds that cause difficulty in treatment (backgrounds), important clinical factors and important clinical strategies. Statistical comparisons were made between the groups. In the Likert scale, higher scores show a greater degree of difficulty. RESULTS: We obtained responses from 439 and 397 specialists in the G and PC, respectively (response rates 26.6 and 24.1%). The overall scores for "diseases" and "backgrounds" were significantly higher in the G than those in the PC (P < 0.001 and P = 0.018). The top 10 items in the "backgrounds" and in the "important clinical strategies" were all matched between the groups. The overall score of the "important clinical factors" was not statistically different between the groups; however, "low nutrition," "bedridden activities of daily living," "living alone" and "frailty" were found only in the top 10 items of the G, and "financial problems" was found in those of the PC. CONCLUSIONS: Geriatricians and primary care physicians have many similarities and differences in their approaches to multimorbidity management. Therefore, there is an urgent need to establish a system in which they can share a common understanding to manage older patients with multimorbidity. Geriatr Gerontol Int 2023; 23: 628-638.

Psychometrics of the kiddie schedule for affective disorders and schizophrenia present and lifetime version for DSM-5 in Japanese outpatients.

OBJECTIVE: The Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version (K-SADS-PL) is a widely used semi-structured diagnostic interview in child and adolescent psychiatry. However, the psychometric properties of its updated version, the K-SADS-PL for DSM-5, have scarcely been examined, especially for criterion validity. This study was designed to examine the inter-rater reliability, criterion validity and construct validity of the K-SADS-PL for DSM-5 in 137 Japanese outpatients. METHODS: Two of 12 experienced clinicians independently performed the K-SADS interview for each patient in a conjoint session, and the resulting consensus diagnosis was compared with a "best-estimate" diagnosis made by two of eight experienced clinicians using all available information for the patient. RESULTS: The inter-rater reliability was excellent, as shown by κ > 0.75 for all disorders, with the exception of current separation anxiety disorder. The criterion validity was fair to good, as shown by κ > 0.40 for all disorders, with the exception of current and lifetime agoraphobia. The construct validity was also good, as shown by theoretically expected associations between the K-SADS-PL diagnoses and subscales of the child behavior checklist. CONCLUSION: The K-SADS-PL for DSM-5, now available in Japanese, generates valid diagnoses in child and adolescent psychiatry.

Practical applications of brief screening questionnaires for autism spectrum disorder in a psychiatry outpatient setting.

OBJECTIVES: This study was designed to examine the diagnostic performance of the social and communication disorders checklist (SCDC) and strength and difficulties questionnaire (SDQ) to detect autism spectrum conditions (ASC), along with the social responsiveness scale-second edition (SRS-2) as reference, in a psychiatry outpatient setting. METHODS: We translated the SCDC into Japanese since its Japanese version was unavailable. We examined its test-retest reliability as well as the internal consistency reliability and diagnostic performance of the three questionnaires among 41 Japanese psychiatric outpatients, using the best-estimate diagnosis of ASC based on the diagnostic interview for social and communication disorders, as a gold standard. RESULTS: The test-retest reliability was high for the SCDC. Although the internal consistency reliability was high for the SCDC and SRS-2, that was low for the prosocial and peer problem subscales of the SDQ. The performance of the SCDC, SDQ, and SRS-2 to detect ASC was moderate: the area under the ROC curve of 0.78, 0.78, and 0.84, respectively. CONCLUSIONS: Although questionnaires to detect ASC, including the three examined, generally have only moderate performance in this setting, these can be successfully applied to high-risk populations such as psychiatry outpatients, when multi-level rather than dichotomous likelihood ratios are used.

[Infectious endocarditis due to Gemella morbillorum found by splenic infarction--a case report].

A 64-year-old man with prostate cancer and bone metastasis admitted for nausea, left abdominal pain showed no abnormal, and fever, abdominal ultrasound or chest X-ray findings. Despite antibiotics, left abdominal pain persisted for several days. Abdominal computed tomography (CT), showed splenic infarction. Transesophageal echocardiography suggested infectious endocarditis (IE) as a possible infarction cause, and roth spots were found on the retina. Gemella morbillorum was detected from blood culture. IE commonly causes Fever of Unknown Origin found by infarction. G. morbillorum, an anaerobic gram-positive, viridans group streptococci, is indigenous to the oropharynx, upper respiratory, urogenital, and gastrointestinal tracts, and is thought to have weak toxicity and pathogenicity in the body.

How Does Work Motivation Impact Employees' Investment at Work and Their Job Engagement? A Moderated-Moderation Perspective Through an International Lens.

This paper aims at shedding light on the effects that intrinsic and extrinsic motivation, as predictors, have on heavy work investment of time and effort and on job engagement. Using a questionnaire survey, this study conducted a moderated-moderation analysis, considering two conditional effects-worker's status (working students vs. non-student employees) and country (Israel vs. Japan)-as potential moderators, since there are clear cultural differences between these countries. Data were gathered from 242 Israeli and 171 Japanese participants. The analyses revealed that worker's status moderates the effects of intrinsic and extrinsic motivation on heavy work investment of time and effort and on job engagement and that the moderating effects were conditioned by country differences. Theoretical and practical implications and future research suggestions are discussed.

Experiences of Negotiations for Improving Research Environment and Burnout among Young Physician Researchers in Japan.

Physician scientists in Japan are often too busy to be sufficiently involved in research work. This cross-sectional study aimed to investigate their experiences negotiating with their superiors to improve their research environment and determine its relationship with psychological burnout. Among 1790 physician awardees of Grants-in-Aid for Young Scientists in 2014-2015, 490 responded (response rate 27.4%) and 408 were eligible for analysis. Outcome measures included two negotiation experiences: for reduction of clinical duty hours/promotion opportunities and for increased space or equipment/increased research budget. The main explanatory variables were personal, patient-related, and work-related burnout measured by the Copenhagen Burnout Inventory. The percentages of the above-mentioned two types of negotiations were 20-24% in women and 17-20% in men. Multivariable stepwise logistic regression analyses demonstrated that (1) the negotiation for reduction of clinical duty hours/promotion opportunities was significantly associated with physician scientists who had a short amount of weekly research time and high patient-related burnout score, and (2) the negotiation for increased space or equipment/increased research budget was significantly associated with older age, single status, and high personal and patient-related burnout scores. High burnout is related to negotiation experiences among physician researchers in Japan.

Penicilliols A and B, novel inhibitors specific to mammalian Y-family DNA polymerases.

Penicilliols A (1) and B (2) are novel 5-methoxy-3(2H)-furanones isolated from cultures of a fungus (Penicillium daleae K.M. Zalessky) derived from a sea moss, and their structures were determined by spectroscopic analyses. These compounds selectively inhibited activities of eukaryotic Y-family DNA polymerases (pols) (i.e., pols eta, iota and kappa), and compound 1 was a stronger inhibitor than compound 2. Among mammalian Y-family pols, mouse pol iota activity was most strongly inhibited by compounds 1 and 2, with IC(50) values of 19.8 and 32.5 microM, respectively. On the other hand, activities of many other pols, such as A-family (i.e., pol gamma), B-family (i.e., pols alpha, delta and epsilon) or X-family (i.e., pols beta, lambda and terminal deoxynucleotidyl transferase), and some DNA metabolic enzymes, such as calf primase of pol alpha, human immunodeficiency virus type-1 (HIV-1) reverse transcriptase, human telomerase, T7 RNA polymerase, mouse IMP dehydrogenase (type II), human topoisomerases I and II, T4 polynucleotide kinase or bovine deoxyribonuclease I, are not influenced by these compounds. In conclusion, this is the first report on potent inhibitors of mammalian Y-family pols.