Associations among plasma markers for N-methyl-d-aspartate receptor hypofunction, redox dysregulation, and insufficient myelination in patients with schizophrenia.

Background: Several hypotheses regarding the pathomechanisms of schizophrenia have been proposed. If schizophrenia is a unitary disease, then these pathological processes must be linked; however, if such links do not exist, schizophrenia may best be considered a group of disorders. Only a few studies have examined the relationships among these pathomechanisms. Herein, we examined the relationships among deficient myelination, NMDA receptor hypofunction, and metabolic dysregulation by measuring various plasma markers and examining their correlations. Methods: Plasma samples were collected from 90 patients with schizophrenia and 68 healthy controls. Concentrations of nardilysin (N-arginine dibasic convertase, NRDC), a positive regulator of myelination, the NMDA receptor co-agonist d-serine and glycine, various additional amino acids related to NMDA receptor transmission (glutamate, glutamine, and l-serine), and homocysteine (Hcy), were measured. Concentrations were compared using independent samples t-test or logistic regression, and associations were evaluated using Pearson's correlation coefficients. Results: Plasma glycine (t = 2.05, p = 0.042), l-serine (t = 2.25, p = 0.027), and homocysteine (t = 3.71, p < 0.001) concentrations were significantly higher in patients with schizophrenia compared to those in healthy controls. Logistic regression models using age, sex, smoking status, glutamine, glutamate, glycine, l-serine, d-serine, homocysteine, and NRDC as independent variables revealed significantly lower plasma d-serine (p = 0.024) and NRDC (p = 0.028), but significantly higher l-serine (p = 0.024) and homocysteine (p = 0.001) in patients with schizophrenia. Several unique correlations were found between NMDA receptor-related amino acids and NRDC in patients with schizophrenia compared to those in healthy controls, while no correlations were found between plasma homocysteine and other markers. No associations were found between plasma marker concentrations and disease status or cognitive function in patients with schizophrenia, except for a significant correlation between plasma glycine and full intelligence quotient. Conclusion: Reduced myelination and NMDA receptor hypofunction may be related to pathological mechanisms in schizophrenia, while homocysteine dysregulation appears to be an independent pathological process. These results suggest that schizophrenia may be a group of disorders with unique or partially overlapping etiologies.

Total Synthesis of (-)-Enigmazole A by the Macrocyclization/Transannular Pyran Cyclization Strategy.

An 18-step synthesis of (-)-enigmazole A is herein disclosed. The present synthesis is based on a modular assembly of three building blocks of similar complexity, a macrocyclic ring-closing metathesis to forge the 18-membered macrocyclic skeleton, and a desilylative transannular oxa-Michael addition for stereoselective construction of the 2,6-cis-substituted tetrahydropyran ring.

Laparoscopic cholecystectomy and common bile duct exploration for gallstone and common bile duct stone in a patient with a left-sided gallbladder: a case report.

Left-sided gallbladder is a rare finding that is mostly discovered incidentally during surgery and is often associated with anatomic anomalies. We herein report a case in which laparoscopic cholecystectomy and common bile duct exploration were achieved for an 89-year-old female patient with left-sided gallbladder. Surgery was carried out using our usual trocar position. Calot triangle was covered by the body of the gallbladder and could not be detected. We dissected the gallbladder from the fundus towards the neck. The cystic duct joined the common bile duct from the right side, and common bile duct exploration was performed routinely without perioperative comorbidities. Although the preoperative diagnosis rate is low and the risk of intraoperative bile duct injuries in patients with left-sided gallbladder is high, laparoscopic cholecystectomy and common bile duct exploration can be safely performed by understanding the location and bifurcation of the cystic duct.

Acute cholecystitis with sepsis due to Edwardsiella tarda: a case report.

BACKGROUND: Edwardsiella tarda (E. tarda) is a Gram-negative facultative anaerobe belonging to Enterobacteriales and is commonly isolated from fishes and reptiles. Infection due to E. tarda is uncommon among humans, with a reported human retention rate of 0.001%. It can cause sepsis in the elderly or those with pre-existing conditions such as liver failure, autoimmune disease, or malignancy. E. tarda is susceptible to many antibiotics; however, a high mortality rate (approximately 40%) has been reported with sepsis. CASE PRESENTATION: A 65-year-old woman presented to our hospital with a chief complaint of fever and abdominal pain for 2 days. Her blood tests showed elevated inflammatory markers, and contrast-enhanced computed tomography showed distention and wall thickening of the gallbladder and inflammation of peri-gallbladder fat. Subsequently, a diagnosis of cholecystitis with systemic inflammatory response syndrome was made. Laparoscopic cholecystectomy was performed after starting antimicrobial therapy. Blood culture of samples obtained on admission were positive for E. tarda, which was also detected in bile juice culture. Therefore, she was diagnosed with bacteremia caused by E. tarda, and postoperative antimicrobial therapy was continued. The patient improved, and there were no complications. CONCLUSIONS: We experienced an extremely rare case of acute cholecystitis caused by E. tarda. Only a few cases of acute cholecystitis due to E. tarda have been reported. Furthermore, similar to this case, no previous study has reported the detection of E. tarda in both blood and bile cultures in acute cholecystitis cases. In addition to appropriate surgical intervention, continuous administration of antibiotics based on culture results resulted in a favorable outcome.

Nonsmoking after simultaneous alcohol abstinence and smoking cessation program was associated with better drinking status outcome in Japanese alcohol-dependent men: A prospective follow-up study.

BACKGROUND: Growing evidence suggests that intervention for smoking cessation enhances alcohol abstinence in treatment settings for alcohol dependence. However, research in this field is rare in Asians. METHOD: We prospectively investigated the association of smoking status with drinking status using 9 surveys mailed during a 12-month period in 198 Japanese alcohol-dependent men (70 never/ex-smokers and 128 smokers) who admitted for the first time and completed a 3-month inpatient program for simultaneous alcohol abstinence and smoking cessation. RESULTS: Nonsmoking during the first month after discharge and at the end of follow-up was reported in 28.9% and 25.0% of the baseline smokers, respectively. Kaplan-Meier estimates showed that a 12-month alcohol abstinence and heavy-drinking-free status were more frequent among never/ex-smokers (45.1% and 59.8%, respectively) and baseline smokers who quit smoking during the first month after discharge (59.0% and 60.8%, respectively), compared with sustained smokers (30.0% and 41.2%, respectively). Among the baseline smokers, the multivariate odds ratio (95% confidence interval) for smoking cessation during the first month were 2.77 (1.01-7.61) for alcohol abstinence during the period and 2.50 (1.00-6.25) for use of varenicline, a smoking cessation agent, during the inpatient program. After adjusting for age, drinking profile, lifestyle, family history of heavy or problem drinking, lifetime episodes of other major psychiatric disorders, and medications at discharge, the multivariate hazard ratios (HRs) for drinking lapse were 0.57 (0.37-0.89) for the never/ex-smoking and 0.41 (0.23-0.75) for new smoking cessation groups, respectively, compared with sustained smoking, while the corresponding HRs for heavy-drinking lapse were 0.55 (0.33-0.90) and 0.47 (0.25-0.88), respectively. The HR for drinking lapse was 0.63 (0.42-0.95) for the nonsmoking group (vs. smoking) during the observation period, while the HR for heavy-drinking lapse was 0.58 (0.37-0.91) for the nonsmoking group (vs. smoking) during the observation period. Other significant variables that worsened drinking outcomes were higher daily alcohol intake prior to hospitalization, family history of heavy or problem drinking and psychiatric medications at discharge. CONCLUSION: Nonsmoking was associated with better outcomes on the drinking status of Japanese alcohol-dependent men, and a smoking cessation program may be recommended to be integrated into alcohol abstinence programs.

[A Case of Resection of Locally Advanced Ascending Colon Cancer in an Elderly Patient with Parkinson's Disease].

The case presented here is of a man in his 80s who was attending the Department of Neurology for Parkinson's disease. He had a fever and visited the emergency department. A CT scan revealed a 10 cm mass in the hepatic flexure that was suspected of invading the duodenum, as well as numerous enlarged lymph nodes around the mass. A colonoscopy revealed a semi-peripheral type 3 tumor, and a biopsy showed adenocarcinoma(tub1-tub2). A right hemicolectomy was performed, and the tumor was located in the hepatic flexure of the ascending colon and was found to be in a mass with lymph nodes and adhesions to the duodenum. Due to the invasiveness of the surgery and the decrease in ADL, the patient's postoperative course required prolonged hospitalization. He was transferred to the hospital at POD33 and discharged at POD64. Due to his old age, adjuvant chemotherapy was not administered, and he is still alive 1 year after surgery with no recurrence. Even though his hospital stay was prolonged due to his decreased ADL, he is now able to return home. Aggressive resection may provide good results even in elderly patients.

Regulator of Awn Elongation 3, an E3 ubiquitin ligase, is responsible for loss of awns during African rice domestication.

Two species of rice have been independently domesticated from different ancestral wild species in Asia and Africa. Comparison of mutations that underlie phenotypic and physiological alterations associated with domestication traits in these species gives insights into the domestication history of rice in both regions. Asian cultivated rice, Oryza sativa, and African cultivated rice, Oryza glaberrima, have been modified and improved for common traits beneficial for humans, including erect plant architecture, nonshattering seeds, nonpigmented pericarp, and lack of awns. Independent mutations in orthologous genes associated with these traits have been documented in the two cultivated species. Contrary to this prevailing model, selection for awnlessness targeted different genes in O. sativa and O. glaberrima. We identify Regulator of Awn Elongation 3 (RAE3) a gene that encodes an E3 ubiquitin ligase and is responsible for the awnless phenotype only in O. glaberrima. A 48-bp deletion may disrupt the substrate recognition domain in RAE3 and diminish awn elongation. Sequencing analysis demonstrated low nucleotide diversity in a ~600-kb region around the derived rae3 allele on chromosome 6 in O. glaberrima compared with its wild progenitor. Identification of RAE3 sheds light on the molecular mechanism underlying awn development and provides an example of how selection on different genes can confer the same domestication phenotype in Asian and African rice.

A case of perforated immune-related colitis complicated by cytomegalovirus infection during treatment of immune-related adverse effect in lung cancer immunotherapy.

Although immune checkpoint inhibitors (ICIs) can be used for lung cancer treatment, the activated immune response may cause immune-related adverse effects (irAEs). We present here a case of cytomegalovirus (CMV) enterocolitis during steroid therapy for an irAE. A 70-year-old man diagnosed with small-cell lung carcinoma (limited disease) received radiotherapy plus two chemotherapy cycles of cisplatin and etoposide. The tumor exhibited complete response but recurred after 3 years. After treatment with two cycles of carboplatin, etoposide, and atezolizumab, an inhibitors of programmed cell death receptor-1, he was switched to atezolizumab every 3 weeks for maintenance therapy. Diarrhea occurred after nine atezolizumab doses. With a strong suspicion of ICI-induced colitis, we administered methylprednisolone 500 mg for 3 days, followed by oral prednisolone 40 mg/day. Total colonoscopy during the treatment revealed mucosal inflammation of the total colon, suggesting immune-related colitis. Biopsies from the ulceration revealed crypt abscess with highly infiltrative plasma cells and lymphocytes. Furthermore, immunohistochemical staining showed positivity for CMV. With no improvement in watery diarrhea, the prednisolone dose was increased to 80 mg/day on the 11th day, and ganciclovir was additionally administered twice daily on the 26th day. On the 28th day, the patient had abdominal pain, and abdominal computed tomography revealed free air, resulting in the diagnosis of colon perforation. He underwent subtotal colectomy followed by ileostomy as emergency surgery. A colon specimen revealed colitis with CMV infection. We describe colon perforation in a patient with CMV enterocolitis complicated by refractory immune-related colitis.

[Two Cases of Aortitis Caused by Pegfilgrastim Administered during Chemotherapy for Breast Cancer].

Granulocyte colony-stimulating factor(G-CSF)is known to cause bone pain, headache, and fatigue as side effects. We experienced 2 cases of aortitis caused by pegfilgrastim(PEG-G)administration. Case 1: A 50s woman with breast cancer started FEC therapy with PEG-G as neoadjuvant chemotherapy. She developed a fever in the 38℃ range, and chest CT showed wall thickening in the aortic arch. She was diagnosed with aortitis and administration of prednisolone was started, and the fever resolved and the general condition improved dramatically. Case 2: A 70s woman was started TC therapy with PEG-G as adjuvant chemotherapy after surgery. Fever, anorexia, and epigastralgia appeared. A CT scan of the abdomen revealed thickening of the abdominal aortic wall from the thoracoabdominal transition area to the renal artery bifurcation. She was diagnosed with PEG-G-induced aortitis, and administration of prednisolone was started. The fever resolved and the pain disappeared. Although the symptoms of G-CSF-induced aortitis are nonspecific, it is relatively easy to diagnose by CT and should be considered when a fever develops after G-CSF administration.

Influence of ADHD, especially attention-deficit characteristics, on the course of alcohol-dependent individuals.

BACKGROUND: While several studies have revealed that neurodevelopmental disorders have a high probability of overlapping with substance use disorders, the effects of neurodevelopmental disorders on the courses of substance use disorders have hardly been examined. METHODS: This study targeted 637 alcohol-dependent individuals who received inpatient treatment and whose drinking situations were followed for 12 months after hospital discharge using mailed questionnaires. The comorbidity of psychiatric disorders and the characteristics associated with the neurodevelopmental disorders were assessed using several measurements at the time of hospital admission. The effects of neurodevelopmental disorders on the drinking courses of the subjects were then estimated. RESULTS: The presence of a current depressive episode or any anxiety disorder significantly lowered the abstinence rates during the follow-up period (p = 0.0195 and p = 0.0214, respectively). ADHD traits as assessed using the ADHD Self-report Scale (ASRS) predicted a significantly poorer abstinence rate (p = 0.0296). Similarly, attention-deficit characteristics assessed objectively through interviews predicted a significantly lower abstinence rate (p = 0.0346), and a sensitivity analysis enhanced these results (p = 0.0019). When the drinking patterns were classified into three groups, the subjects with attention-deficit characteristics had a significantly higher rate of "Recurrence" and lower rates of "Abstinence" and "Controlled drinking" (p = 0.013). In a multivariate proportional hazards analysis, the ASRS score was significantly correlated with the re-drinking risk (p = 0.003). CONCLUSION: ADHD traits had significant effects on not only abstinence rates, but also on drinking pattern. The presence of ADHD traits, especially attention-deficit characteristics, influenced the drinking courses of alcohol-dependent individuals after hospital treatment.

Spontaneous colonic perforation with collagenous colitis in an elderly patient.

Collagenous colitis (CC) is a variant of microscopic colitis that causes chronic, non-bloody, and watery diarrhea. The natural history of CC is generally benign and serious complications are rare. Perforation, especially spontaneous perforation, is a particularly rare complication. A 90-year-old woman presented with acute abdominal pain. She was diagnosed with peritonitis due to colonic perforation, and partial colectomy was performed. Macroscopic findings showed well-circumscribed longitudinal ulcer, and a pathological examination revealed descending colon perforation with CC. She had no history of examination and the case was considered to be spontaneous. The postoperative course was uneventful and she had no recurrence of CC after changing from the suspected drug (lansoprazole) to an H2-blocker. The characteristics of perforation by CC are characteristic longitudinal ulcer and micro-perforation. If it can be diagnosed accurately, conservative treatment may be an option. In spontaneous cases, the history of medication and the site of perforation may assist in this decision.

Accidental duodenal foreign body of toothbrush removed laparoscopically: a case report.

BACKGROUND: Foreign body ingestion is a common case in daily medical care, and it usually passes through the entire gastrointestinal tract naturally and is excreted in the feces. However, long and sharp foreign bodies may be difficult to pass naturally due to their shape. Here, we present a rare case of a duodenal foreign body, a toothbrush, that required laparoscopic surgical removal after a failed endoscopic attempt. CASE PRESENTATION: A 51-year-old male with intellectual disability presented to our hospital due to fever. Initially, he was diagnosed with aspiration pneumonia by chest X-ray and blood examination. However, abdominal X-ray examination suggested a foreign body, and a computed tomography scan revealed a toothbrush in the duodenum. Therefore, upper gastrointestinal endoscopy was immediately attempted to remove it, but it could not be safely removed because the handle part of the toothbrush seemed deeply embedded in the duodenal mucosa. Therefore, this case was diagnosed as duodenal incarceration of the toothbrush, and it was removed by laparoscopic surgery. The operation was performed safely, and the patient's postoperative course was good without any complications. The extracted toothbrush was 15 cm in length. CONCLUSION: We experienced a rare case of a duodenal foreign body, which was a toothbrush. The duodenal foreign body was safely removed by laparoscopic surgery for the first time.

Stereoselective Tandem Synthesis of Pyrrolidine Derivatives under Gold Catalysis: An Asymmetric Synthesis of (-)-Lepadiformine A.

A Au-catalyzed tandem alkyne hydroamination/iminium ion formation/allylation reaction was developed for expedient access to pyrrolidine derivatives bearing a tetrasubstituted carbon stereocenter. The tandem reaction was successfully applied to a 12-step asymmetric synthesis of (-)-lepadiformine A, a marine cytotoxic tricyclic alkaloid.

Toe grip force of the dominant foot is associated with fall risk in community-dwelling older adults: a cross-sectional study.

BACKGROUND: It is unclear whether the toe grip force (TGF) of the dominant foot (DF) and the lower limb function asymmetry (LLFA) in older adults are associated with fall risk. Therefore, this study aimed to investigate the effect of lower limb properties (such as TGF, muscle strength, and plantar sensation) on the risk of falls in older adults, while considering the foot dominance and asymmetry of lower limb function. METHODS: This study was a cross-sectional study. We determined whether the lower limb function of the DF and non-dominant foot (non-DF) and LLFA had any effect on the fall risk in 54 older adults (mean ± standard deviation: 72.2 ± 6.0, range: 60-87 years). We examined the participants' fall history, Mini-Mental State Examination (MMSE) score, lower limb function, and LLFA. To determine fall risk factors, we performed logistic regression analysis, with presence or absence of falls as the dependent variable. RESULTS: The independent variables were age, sex, MMSE score, two-point discrimination of the heel (non-DF) as plantar sensation index, and the TGF of both feet. Only the TGF of the DF was identified as a risk factor for falls (p < 0.05). CONCLUSIONS: In older adults, clinicians should focus on the TGF of the DF as a risk factor for falls. TRIAL REGISTRATION: This study was retrospectively registered. https://center6.umin.ac.jp/cgi-bin/ctr/ctr_up_rec_f1.cgi .

Periocular Skin Warming Promotes Sleep Onset Through Heat Dissipation From Distal Skin in Patients With Insomnia Disorder.

Study Objectives: Periocular skin warming before bedtime has been demonstrated to improve subjective sleep initiation in healthy adults with sleep difficulties scored six or higher in the Pittsburgh Sleep Questionnaire Index. This study aimed to investigate the effects of periocular skin warming on sleep initiation and thermoregulation processes in patients with insomnia disorder. Methods: Participants included those with sleep difficulty (n = 22) and those with insomnia disorder (n = 16). Individuals from both groups were assessed at baseline (habitual sleep-wake schedule) and after two intervention conditions (use of a warming eye mask or a sham eye mask before habitual bedtime). The subjective and electroencephalographic sleep onset latency, along with proximal and distal skin temperature after periocular skin warming, were evaluated. Results: Periocular skin warming reduced objective sleep onset latency in independently of the group. Foot temperature and foot-proximal temperature gradient after getting into bed increased with periocular skin warming in independently of the group. However, the increase in hand temperature was observed only in the insomnia disorder group. Periocular skin warming also increased the normalized high frequency component of heart rate variability in independently of the group. The reduction of objective sleep onset latency was strongly associated with heat dissipation from the foot skin region. Conclusion: These results suggest that periocular skin warming promotes sleep initiation by enhancing heat dissipation from the distal skin regions in individuals with sleep difficulty and insomnia disorder. Periocular skin warming could thus be a novel non-pharmacological therapy for insomnia disorder.

[A Case in Which Inferior Vena Cava Stent Placement Was Effective for Inferior Vena Cava Stenosis Due to Metastatic Liver Tumor].

A 60s woman was diagnosed with cecal cancer with multiple liver metastases(final pathology was T4aN1M1[H1])and underwent ileocecal resection and D3 dissection. She did not wish for postoperative chemotherapy and surgical treatment of liver metastases. One and a half years after surgery, she developed extremity edema of lower legs and hypoalbuminemia, and she gained 20 kg. Contrast-enhanced CT showed stenosis of the inferior vena cava due to liver metastases, which was markedly improved the symptoms by placement of an inferior vena cava stent. Inferior vena cava stent placement is a minimally invasive treatment and can be an option as it can be expected to improve quality of life in some cases.

Loss of OsEAF6, a Subunit of the Histone Acetyltransferase Complex, Causes Hybrid Breakdown in Intersubspecific Rice Crosses.

Gene duplication plays an important role in genetic diversification, adaptive evolution, and speciation. Understanding the mechanisms and effects of postzygotic isolation genes is important for further studies of speciation and crop breeding. The duplicate recessive genes hwe1 and hwe2 cause hybrid breakdown, characterized by poor vegetative growth and reproductive dysgenesis in intersubspecific crosses between Oryza sativa ssp. indica and japonica. Using a map-based cloning strategy, we found that HWE1 and HWE2 encode the Esa1-associated factor 6 (EAF6) protein, a component of histone acetyltransferase complexes. The indica hwe1 and japonica hwe2 alleles lacked functional EAF6, demonstrating that the double recessive homozygote causes hybrid breakdown. Morphological and physiological observations showed that weak plants with double recessive homozygotes had serious morphological defects with a wide range of effects on development and organs, leading to leaves with reduced chlorophyll content, flower and pistil malformation, and anomalies of gametogenesis. These findings suggest that EAF6 plays a pivotal role in the transcriptional regulation of essential genes during the vegetative and reproductive development of rice.

[Eight Cases of Breast Cancer That Relapsed More Than Ten Years after Initial Treatment].

Recurrence is more common for breast cancer than other solid tumors. In the last 5 years, we experienced 8 cases that relapsed more than 10 years after initial treatment. All cases were hormone-sensitive and HER2-negative. The Ki-67 percentage score was less than 15% in 7 cases. The age range at recurrence was 56-93 years(mean, 74.6 years), and the time to recurrence was 10-14 years and 20 or more years in 6 and 2 cases(mean, 14.6 years), respectively. The triggers for diagnosis were subjective symptoms, follow-up, and examination for other diseases in 3, 3, and 2 cases, respectively. The recurrence sites included the axilla, pleura/lung, liver/lung, skin, and chest wall in 3, 2, 1, 1, and 1 case, respectively. Treatment included an aromatase inhibitor(AI)and AI plus CDK4/6 inhibitor in 5 and 3 cases, respectively. The post-recurrence treatment period was 6-31 months(mean, 21.6 months), with 4 cases of PR, 3 cases of SD, and 1 case of death from other disease. There were 3 cases of axillary recurrence and 1 case each of neuropathic pain, upper limb edema, and local pain; all were alleviated by the treatment. In 2 cases, the pleural effusion decreased without chest tube drainage. Hormone receptor- positive late-relapse cases are generally highly therapeutically sensitive with favorable prognosis. In many cases, AI alone was selected considering patient age, side effects, treatment costs, and other factors.

Alcohol dependence severity determines the course of treatment-seeking patients.

BACKGROUND: While accumulating evidence suggests a relation between the severity of alcohol dependence and the risk of its recurrence, the impact of dependence severity on the course of the disorder has not been carefully evaluated. The present study examined the impact of several severity indices of alcohol dependence on the drinking course after inpatient treatment. METHODS: This prospective study was conducted over a 12-month period following alcohol treatment at a specialized hospital. A total of 712 consecutively admitted alcohol-dependent patients were targeted for enrollment at the time of their hospitalization, with 637 patients registered and followed. The characteristics and severity of the subjects were assessed using multiple methods at admission, with their course after discharge followed continuously using mailed questionnaires that queried them regarding their drinking behavior. RESULTS: Greater severity of dependence, assessed using the number of ICD-10 diagnostic criteria met, was associated with a lower rate of abstinence during the study period (p = 0.035). The rate of abstinence also decreased significantly as the baseline blood gamma-glutamyl transferase value and Alcohol Dependence Scale (ADS) score increased (p = 0.031 and p = 0.0002, respectively). In multivariate Cox proportional hazards analyses, the group with the most severe ADS scores had a significantly greater risk of relapse to drinking than the group with the least severe scores (HR = 2.67, p = 0.001). Dependence severity also associated with the drinking pattern; participants in both the controlled drinking group and the abstinence group had lower ADS scores at admission and a later age at first drinking (p = 0.001 and p < 0.001, respectively) than those with poorer drinking outcomes. CONCLUSIONS: The present study showed that more severe alcohol dependence predicts a poorer course after alcohol treatment, as reflected by findings on multiple measures. These results suggest that assessing the dependence severity at the outset of treatment could be useful both in predicting treatment outcome and targeting interventions to alcohol-dependent individuals who need additional support in their recovery.