OBJECTIVE

To establish, in a single resource, up-to-date recommendations for primary care physicians regarding prevention strategies for a first stroke.

METHODS

Members of the National Stroke Association's (NSA's) Stroke Prevention Advisory Board and Cedars-Sinai Health System Department of Health Services Research convened on April 9, 1998, in an open meeting. The conference attendees, selected to participate by the NSA, were recognized experts in neurology (9), cardiology (2), family practice (1), nursing (1), physician assistant practices (1), and health services research (2).

METHODS

A literature review was carried out by the Department of Health Services Research, Cedars-Sinai Health System, Los Angeles, Calif, using the MEDLINE database search for 1990 through April 1998 and updated in November 1998. English-language guidelines, statements, meta-analyses, and overviews on prevention of a first stroke were reviewed.

METHODS

At the meeting, members of the advisory board identified 6 important stroke risk factors (hypertension, myocardial infarction [MI], atrial fibrillation, diabetes mellitus, blood lipids, asymptomatic carotid artery stenosis), and 4 lifestyle factors (cigarette smoking, alcohol use, physical activity, diet).

CONCLUSIONS

Several interventions that modify well-documented and treatable cardiovascular and cerebrovascular risk factors can reduce the risk of a first stroke. Good evidence for direct stroke reduction exists for hypertension treatment; using warfarin for patients after MI who have atrial fibrillation, decreased left ventricular ejection fraction, or left ventricular thrombus; using 3-hydroxy-3 methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors for patients after MI; using warfarin for patients with atrial fibrillation and specific risk factors; and performing carotid endarterectomy for patients with stenosis of at least 60%. Observational studies support the role of modifying lifestyle-related risk factors (eg, smoking, alcohol use, physical activity, diet) in stroke prevention. Measures to help patients improve adherence are an important component of a stroke prevention plan.

The molecular requirements for invariant Valpha14-bearing natural killer T cells (iNKT) in the thymus are poorly understood. A minute population of approximately 500 newly selected CD69(+)CD24(+) stage 0 (ST0) iNKT cells gives rise to approximately 100 times more CD44(neg/lo)CD24(-) stage 1 (ST1) cells, which then generate similar frequencies of CD44(hi)CD24(-) stage 2 (ST2) and mature iNKT cells. Although the increased number of ST1 compared with ST0 cells indicates the initiation of a proliferation wave in the very early stages of iNKT cell development, details about the controlling mechanism are currently lacking. Here, we show that the transcription factor c-Myc is required for iNKT cell development. Conditional ablation of c-Myc in double-positive thymocytes specifically impacted iNKT but not conventional T cell development. Within the iNKT population, a progressive reduction of iNKT cells was observed starting at ST1 (approximately 50-fold) and ST2 (approximately 350-fold), with a complete lack of mature cells in thymus, spleen, and liver. ST0/ST1 c-Myc-deficient iNKT cells showed reduced proliferation. In contrast, annexin V staining did not reveal increased apoptosis, and transgenic overexpression of BCL-2 did not rescue iNKT cell development in c-Myc-deficient mice. Moreover, expression of known iNKT differentiation factors such as Plzf and Gata3 was not dramatically altered. These, findings provide compelling evidence that c-Myc mediates an intrathymic proliferation wave immediately after agonist selection of iNKT cells and illustrate the importance of this expansion for the generation of mature iNKT cells in vivo.

Neisseria meningitidis (the meningococcus) causes significant morbidity and mortality in children and young adults worldwide through epidemic or sporadic meningitis and/or septicemia. In this review, we describe the biology, microbiology, and epidemiology of this exclusive human pathogen. N.meningitidis is a fastidious, encapsulated, aerobic gram-negative diplococcus. Colonies are positive by the oxidase test and most strains utilize maltose. The phenotypic classification of meningococci, based on structural differences in capsular polysaccharide, lipooligosaccharide (LOS) and outer membrane proteins, is now complemented by genome sequence typing (ST). The epidemiological profile of N. meningitidis is variable in different populations and over time and virulence of the meningococcus is based on a transformable/plastic genome and expression of certain capsular polysaccharides (serogroups A, B, C, W-135, Y and X) and non-capsular antigens. N. meningitidis colonizes mucosal surfaces using a multifactorial process involving pili, twitching motility, LOS, opacity associated, and other surface proteins. Certain clonal groups have an increased capacity to gain access to the blood, evade innate immune responses, multiply, and cause systemic disease. Although new vaccines hold great promise, meningococcal infection continues to be reported in both developed and developing countries, where universal vaccine coverage is absent and antibiotic resistance increasingly more common.

Osteoblasts expressing the homophilic adhesion molecule N-cadherin form a hematopoietic stem cell (HSC) niche. Therefore, we examined how N-cadherin expression in HSCs relates to their function. We found that bone marrow (BM) cells highly expressing N-cadherin (N-cadherin(hi)) are not stem cells, being largely devoid of a Lineage(-)Sca1(+)cKit(+) population and unable to reconstitute hematopoietic lineages in irradiated recipient mice. Instead, long-term HSCs form distinct populations expressing N-cadherin at intermediate (N-cadherin(int)) or low (N-cadherin(lo)) levels. The minority N-cadherin(lo) population can robustly reconstitute the hematopoietic system, express genes that may prime them to mobilize, and predominate among HSCs mobilized from BM to spleen. The larger N-cadherin(int) population performs poorly in reconstitution assays when freshly isolated but improves in response to overnight in vitro culture. Their expression profile and lower cell-cycle entry rate suggest N-cadherin(int) cells are being held in reserve. Thus, differential N-cadherin expression reflects functional distinctions between two HSC subpopulations.

In response to an elevated metabolic rate ((.-)V(O(2)), increased microvascular blood-muscle O(2) flux is the product of both augmented O(2) delivery ((.-)Q(O(2)), and fractional O(2) extraction. Whole body and exercising limb measurements demonstrate that (.-)Q(O(2) and fractional O(2) extraction increase as linear and hyperbolic functions, respectively, of (.-)V(O(2). Given the presence of disparate vascular control mechanisms among different muscle fibre types, we tested the hypothesis that, in response to muscle contractions, (.-)Q(O(2) would be lower and fractional O(2) extraction (as assessed via microvascular O(2) pressure, P(mvO(2))) higher in fast- versus slow-twitch muscles. Radiolabelled microsphere and phosphorescence quenching techniques were used to measure (.-)Q(O(2) and P(mvO(2)), respectively at rest and across the transition to 1 Hz twitch contractions at low (Lo, 2.5 V) and high intensities (Hi, 4.5 V) in rat (n = 20) soleus (Sol, slow-twitch, type I), mixed gastrocnemius (MG, fast-twitch, type IIa) and white gastrocnemius (WG, fast-twitch, type IIb) muscle. At rest and for Lo and Hi (steady-state values) transitions, P(mvO(2)) was lower (all P < 0.05) in MG (mmHg: rest, 22.5 +/- 1.0; Lo, 15.3 +/- 1.3; Hi, 10.2 +/- 1.6) and WG (mmHg: rest, 19.0 +/- 1.3; Lo, 12.2 +/- 1.1; Hi, 9.9 +/- 1.1) than in Sol (rest, 33.1 +/- 3.2 mmHg; Lo, 19.0 +/- 2.3 mmHg; Hi, 18.7 +/- 1.8 mmHg), despite lower (.-)V(O(2) and (.-)Q(O(2) in MG and WG under each set of conditions. These data suggest that during submaximal metabolic rates, the relationship between (.-)Q(O(2) and O(2) extraction is dependent on fibre type (at least in the muscles studied herein), such that muscles comprised of fast-twitch fibres display a greater fractional O(2) extraction (i.e. lower P(mvO(2))) than their slow-twitch counterparts. These results also indicate that the greater sustained P(mvO(2)) in Sol may be important for ensuring high blood-myocyte O(2) flux and therefore a greater oxidative contribution to energetic requirements.

Prolonged inhibition of the kinase, mammalian target of rapamycin (mTOR), during myeloid dendritic cell (DC) generation confers resistance to maturation. Recently, however, mTOR inhibition immediately before Toll-like receptor ligation has been found to exert proinflammatory effects on myeloid cells, notably enhanced IL-12p40/p70 production. We show, for the first time, that mouse or human DCs generated under mTOR inhibition exhibit markedly enhanced IL-12p70 production after lipopolysaccharide (LPS) stimulation, despite impaired costimulatory molecule expression and poor T-cell stimulatory ability. Consistent with this finding, we reveal that increased IL-12p40 production occurs predominantly in CD86(lo) immature DCs. High IL-12p40/p70 production by CD86(lo) DC resulted from failed down-regulation of glycogen synthase kinase-3 (GSK-3) activity and could not be ascribed to enhanced Akt function. Despite high IL-12p70 secretion, rapamycin-conditioned, LPS-stimulated DCs remained poor T-cell stimulators, failing to enhance allogeneic Th1 cell responses. We also report that inhibition of GSK-3 impedes the ability of LPS-stimulated DCs to induce forkhead box p3 in CD4(+)CD25(-) T cells, as does the absence of IL-12p40/p70. Thus, GSK-3 activity in DC is regulated via signaling linked to mTOR and modulates their capacity both to produce IL-12p40/p70 and induce forkhead box p3 in CD4(+) T cells under inflammatory conditions.

OBJECTIVE

To quantify the appropriateness of medication prescriptions in nursing home residents.

METHODS

Prospective, cohort study.

METHODS

Twelve nursing homes in the greater Los Angeles area.

METHODS

A total of 1106 nursing home residents.

METHODS

The appropriateness of medication prescriptions was evaluated using explicit criteria developed through consensus by 13 experts from the United States and Canada. These experts identified 19 drugs that should generally be avoided and 11 doses, frequencies, or durations of use of specific drugs that generally should not be exceeded.

RESULTS

Based on the consensus criteria, 40% of residents received at least one inappropriate medication order, and 10% received two or more inappropriate medication orders concurrently; 7% of all prescriptions were inappropriate. Physicians prescribed a greater number of inappropriate medications for female residents. Regression analysis, corrected for clustering effects within facilities, showed that a greater number of inappropriate medication prescriptions were ordered in larger nursing homes. Inappropriate prescriptions were not related to the proportion of Medicaid (Medi-Cal) residents or the number of physicians practicing in the homes.

CONCLUSIONS

Inappropriate medication prescribing in nursing homes is common. Female residents and residents of large nursing homes are at the greatest risk for receiving an inappropriate prescription.

Diesel exhaust particles (DEP) have been implicated in the increased incidence of allergic airway disorders. We investigated the effects of DEP on localized immunoglobulin production by performing nasal challenges with varying doses of DEP and analyzing the local immune response in nasal lavages obtained before and after. A significant rise in nasal IgE but not IgG, IgA, IgM, or albumin was observed in subjects 4 d after challenge with 0.30 mg DEP, equivalent to exposure on an average Los Angeles day. Direct evidence for DEP-enhanced local production of IgE was that challenge increased the number of IgE-secreting cells in lavage fluid from < 1 in 2,000,000 to>> 1 in 100,000 but did not alter the number of IgA-secreting cells. There was a concomitant increase in epsilon mRNA production in the lavage cells. Additionally, DEP altered the relative amounts of five different epsilon mRNAs generated by alternative splicing, mRNAs that code for different IgE proteins. These results show that DEP exposure in vivo causes both quantitative and qualitative changes in local IgE production. The implication is that natural exposure to DEP may result in increased expression of respiratory allergic disease.

The tissue composition of polyunsaturated fatty acids is important to health and depends on both dietary intake and metabolism controlled by genetic polymorphisms that should be taken into consideration in the determination of nutritional requirements. Therefore at the same dietary intake of linoleic acid (LA) and alpha-linolenic acid (ALA), their respective health effects may differ due to genetic differences in metabolism. Delta-5 and delta-6 desaturases, FADS1 and FADS2, respectively, influence the serum, plasma and membrane phospholipid levels of LA, ALA and long-chain polyunsaturated fatty acids during pregnancy, lactation, and may influence an infant's IQ, atopy and coronary heart disease (CHD) risk. At low intakes of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), polymorphisms at the 5-lipoxygenase (5-LO) level increase the risk for CHD whereas polymorphisms at cyclooxgenase-2 increase the risk for prostate cancer. At high intakes of LA the risk for breast cancer increases. EPA and DHA influence gene expression. In future, intervention studies on the biological effects of LA, ALA and LC-PUFAs, and the effects of genetic variants in FADS1 and FADS2, 5-LO and cyclooxygenase-2 should be taken into consideration both in the determination of nutritional requirements and chronic disease risk. Furthermore, genome-wide association studies need to include environmental exposures and include diet in the interaction between genetic variation and disease association.

BACKGROUND

Social networking technologies are an emerging tool for HIV prevention.

OBJECTIVE

To determine whether social networking communities can increase HIV testing among African American and Latino men who have sex with men (MSM).

METHODS

Randomized, controlled trial with concealed allocation. (ClinicalTrials.gov: NCT01701206).

METHODS

Online.

METHODS

112 MSM based in Los Angeles, more than 85% of whom were African American or Latino.

METHODS

Sixteen peer leaders were randomly assigned to deliver information about HIV or general health to participants via Facebook groups over 12 weeks. After participants accepted a request to join the group, participation was voluntary. Group participation and engagement were monitored. Participants could request a free, home-based HIV testing kit and completed questionnaires at baseline and 12-week follow-up.

METHODS

Participant acceptance of and engagement in the intervention and social network participation, rates of home-based HIV testing, and sexual risk behaviors.

RESULTS

Almost 95% of intervention participants and 73% of control participants voluntarily communicated using the social platform. Twenty-five of 57 intervention participants (44%) requested home-based HIV testing kits compared with 11 of 55 control participants (20%) (difference, 24 percentage points [95% CI, 8 to 41 percentage points]). Nine of the 25 intervention participants (36%) who requested the test took it and mailed it back compared with 2 of the 11 control participants (18%) who requested the test. Retention at study follow-up was more than 93%.

CONCLUSIONS

Only 2 Facebook communities were included for each group.

CONCLUSIONS

Social networking communities are acceptable and effective tools to increase home-based HIV testing among at-risk populations.

BACKGROUND

National Institute of Mental Health.

OBJECTIVE

ICU delirium is common and adverse. The Intensive Care Delirium Screening Checklist (ICDSC) score ranges from 0 to 8, with a score of 4 or higher indicating clinical delirium. We investigated whether lower (subsyndromal) values affect outcome.

METHODS

600 patients were evaluated with the ICDSC every 8[Symbol: see text]h.

RESULTS

Of 558 assessed patients 537 noncomatose patients were divided into three groups: no delirium (score = 0; n = 169, 31.5%), subsyndromal delirium (score = 1-3; n = 179, 33.3%), and clinical delirium (score>>or=4; n = 189, 35.2%). ICU mortality rates were 2.4%, 10.6%, and 15.9% in these three groups, respectively. Post-ICU mortality was significantly greater in the clinical delirium vs. no delirium groups (hazard ratio = 1.67) after adjusting for age, APACHE II score, and medication-induced coma. Relative ICU length of stay was: no delirium < subsyndromal delirium < clinical delirium and hospital LOS: no delirium < subsyndromal delirium approximately clinical delirium. Patients with no delirium were more likely to be discharged home and less likely to need convalescence or long-term care than those with subsyndromal delirium or clinical delirium. ICDSC score increments higher than 4/8 were not associated with a change in mortality or LOS.

CONCLUSIONS

Clinical delirium is common, important and adverse in the critically ill. A graded diagnostic scale permits detection of a category of subsyndromal delirium which occurs in many ICU patients, and which is associated with adverse outcome.

Regulatory T cells (Tregs) are crucial for the induction and maintenance of self-tolerance and are present in peripheral tissues such as skin and gut under normal, noninflamed conditions. We report isolation and expansion of the Treg population resident in normal human skin. Cutaneous Tregs expressed high levels of CD25, L-selectin, GITR, FOXP3, and intracellular CTLA-4, low levels of CD69, and high levels of the skin-homing addressins CLA, CCR4, and CCR6. Skin Tregs suppressed the proliferation of CD25(lo) T cells from the same skin sample in response to CD3 and CD28 antibodies. Suppression was dependent on cell contact and not affected by neutralizing antibodies to interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta). Surprisingly, cutaneous Tregs proliferated in an antigen-independent manner when cultured in contact with dermal fibroblasts and IL-15, conditions similar to those found in chronically inflamed skin. We hypothesize that local proliferation of Tregs may occur within inflamed skin and could serve as a brake for cutaneous inflammation as well as a mechanism for the homeostatic proliferation of natural Tregs that has been observed within intact organisms.

OBJECTIVE

To evaluate ability of the University of California Los Angeles Integrated Staging System (UISS) to stratify patients with localized and metastatic renal cell carcinoma (RCC) into risk groups in an international multicenter study.

METHODS

4,202 patients from eight international academic centers were classified according to the UISS, which combines TNM stage, Fuhrman grade, and Eastern Cooperative Oncology Group performance status. Distribution of the UISS categories was assessed in the overall population and in each center.

RESULTS

The UISS stratified both localized and metastatic RCC into three different risk groups (P <.001). For localized RCC, the 5-year survival rates were 92%, 67%, and 44% for low-, intermediate-, and high-risk groups, respectively. A trend toward a higher risk of death was observed in all centers for increasing UISS risk category. For metastatic RCC, the 3-year survival rates were 37%, 23%, and 12% for low-, intermediate-, and high-risk groups, respectively; in 6 of 8 centers, a trend toward a higher risk of death was observed for increasing UISS risk category. A greater variability in survival rates among centers was observed for high-risk patients.

CONCLUSIONS

This study defines the general applicability of the UISS for predicting survival in patients with RCC. The UISS is an accurate predictor of survival for patients with localized RCC applicable to external databases. Although the UISS may be useful for patients with metastatic RCC, it may be less accurate in this subset of patients due to the heterogeneity of patients and treatments.

OBJECTIVE

We examined availability and food options at restaurants in less affluent (target area) and more affluent (comparison area) areas of Los Angeles County to compare residents' access to healthy meals prepared and purchased away from home. We also considered environmental prompts that encourage the purchase of various foods.

METHODS

We designed an instrument to assess the availability, quality, and preparation of food in restaurants. We also assessed advertisements and promotions, cleanliness, and service for each restaurant. We assessed 659 restaurants: 348 in the target area and 311 in the comparison area.

RESULTS

The nutritional resource environment in our target area makes it challenging for residents to eat healthy away from home. Poorer neighborhoods with a higher proportion of African American residents have fewer healthy options available, both in food selections and in food preparation; restaurants in these neighborhoods heavily promote unhealthy food options to residents.

CONCLUSIONS

Environment is important in understanding health status: support for the healthy lifestyle associated with lower risks for disease is difficult in poorer communities with a higher proportion of African American residents.

We examined the prevalence of somatization disorder symptoms elicited with the Diagnostic Interview Schedule in 3132 community respondents interviewed in Los Angeles by the Epidemiologic Catchment Area program. The variables age, gender, ethnic background, and the presence of a psychiatric diagnosis significantly influenced the number of somatization symptoms reported. An introductory review on conceptual and nosological aspects of somatization phenomena led to the formulation of a less-restrictive operational definition of the somatizer. We found that 4.4% of the respondents met criteria for this abridged cutoff score of somatization, whereas only 0.03% of the respondents met criteria for the full DSM-III somatization disorder diagnosis. This abridged cutoff score was associated with sociodemographic factors and psychiatric diagnosis in the direction predicted.

We evaluated whether our previous reports of increased postmenopausal breast cancer risk with higher body mass index (BMI) or of reduced premenopausal and postmenopausal breast cancer risk with higher physical activity levels varied according to the tumor's estrogen receptor (ER) and progesterone receptor (PR) status. Participants enrolled in either of two population-based case-control studies in Los Angeles County, California: one of premenopausal women (ages < or = 40 years), and one of postmenopausal women (ages 55-64 years). Case participants were diagnosed for the first time with in situ or invasive breast cancer from 7/1/83 through 12/31/88 (premenopausal women) or from 3/1/87 through 12/31/89 (postmenopausal women). Joint ER/PR status was collected for 424 premenopausal and 760 postmenopausal case participants. The analysis included 714 premenopausal and 1091 postmenopausal age-matched, race-matched (white or Hispanic), parity-matched (premenopausal women only), and residential neighborhood-matched control participants. Among the postmenopausal women, obesity was associated with an increased odds of ER+/PR+ breast cancer (odds ratio, 2.45 for women in the highest versus the lowest body mass index quartile; 95% confidence interval, 1.73-3.47). Body mass index was associated with neither ER-/PR- tumors among the postmenopausal women nor with any ER/PR subgroup among the premenopausal women. For both premenopausal and postmenopausal women, higher recreational physical activity levels >> or = 17.6 MET-hours/week versus no activity) were associated with a 30-60% reduction in risk of nearly all ER/PR subtypes, although the associations were generally of borderline statistical significance. Examining these potentially modifiable breast cancer risk factors by tumor ER and PR status may provide us with greater insight into breast cancer etiology and the mechanisms underlying the risk factor associations.

To identify risk factors for the occurrence of Kaposi's sarcoma and Pneumocystis carinii pneumonia in homosexual men, we conducted a case-control study in New York City, San Francisco, Los Angeles, and Atlanta. Fifty patients (cases) (39 with Kaposi's sarcoma, 8 with pneumocystis pneumonia, and 3 with both) and 120 matched homosexual male controls (from sexually transmitted disease clinics and private medical practices) participated in the study. The variable most strongly associated with illness was a larger number of male sex partners per year (median, 61 for patients; 27 and 25 for clinic and private practice controls, respectively). Compared with controls, cases were also more likely to have been exposed to feces during sex, have had syphilis and non-B hepatitis, have been treated for enteric parasites, and have used various illicit substances. Certain aspects of a lifestyle shared by a subgroup of the male homosexual population are associated with an increased risk of Kaposi's sarcoma and pneumocystis pneumonia.

Leukocyte 12-lipoxygenase (12-LO) gene expression in pancreatic beta cells is upregulated by cytotoxic cytokines like IL-1beta. Recent studies have demonstrated that 12-LO inhibitors can prevent glutamate-induced neuronal cell death when intracellular glutathione stores are depleted. Therefore, 12-LO pathway inhibition may prevent beta-cell cytotoxicity. To evaluate the role of 12-LO gene expression in immune-mediated islet destruction, we used 12-LO knockout (12-LO KO) mice. Male homozygous 12-LO KO mice and control C57BL/6 mice received 5 consecutive daily injections of low-dose streptozotocin to induce immune-mediated diabetes. Fasting serum glucose and insulin levels were measured at 7-day intervals, and the mice were followed up for 28 days. 12-LO KO mice were highly resistant to diabetes development compared with control mice and had higher serum insulin levels on day 28. Isolated pancreatic islets were treated with IL-1beta, TNF-alpha, and IFN-gamma for 18 hours. Glucose-stimulated insulin secretion in cytokine-treated islets from C57/BL6 mice decreased 54% from that of untreated islets. In marked contrast, the same cytokine mix led to only a 26% decrease in islets from 12-LO KO mice. Furthermore, cytokine-induced 12-hydroxyeicosatetraenoic acid (12-HETE) production was absent in 12-LO KO islets but present in C57/BL6 islets. Isolated peritoneal macrophages were stimulated for 48 hours with IFN-gamma + LPS and compared for nitrate/nitrite generation. 12-LO KO macrophages generated 50% less nitrate/nitrite when compared with C57BL/6 macrophages. In summary, elimination of leukocyte 12-LO in mice ameliorates low dose streptozotocin-induced diabetes by increasing islet resistance to cytokines and decreasing macrophage production of nitric oxide.

BACKGROUND

Randomized trials suggest adjuvant chemotherapy is effective for older patients with stage III colon cancer. However, older patients are less likely to receive this therapy than younger patients, perhaps because of concern about adverse effects.

OBJECTIVE

To evaluate adjuvant chemotherapy use and outcomes for older patients with stage III colon cancer from well-defined population-based settings and health care systems.

METHODS

Observational study of adjuvant chemotherapy use and outcomes by age using Poisson regression to estimate the number of adverse events adjusted for demographic and clinical factors, including comorbid illness and specific elements of chemotherapy regimens documented with clinically detailed medical record reviews and patient and surrogate surveys.

METHODS

Five geographically defined regions (Alabama, Iowa, Los Angeles County, northern California, and North Carolina), 5 integrated health care delivery systems, and 15 Veterans Affairs hospitals.

METHODS

Six hundred seventy-five patients diagnosed with stage III colon cancer from 2003 through 2005 who underwent surgical resection and were followed up for as long as 15 months postdiagnosis.

METHODS

Chemotherapy regimen, dose, duration, and annualized mean number of adverse events stratified by age.

RESULTS

Of 202 patients aged 75 years and older, 101 (50%) received adjuvant chemotherapy compared with 87% of 473 younger patients (difference, 37%; 95% confidence interval [CI], 30%-45%). Among patients who received adjuvant chemotherapy, 14 patients (14%) aged 75 years and older and 178 younger patients (44%) received a regimen containing oxaliplatin (difference, 30%; 95% CI, 21%-38%). Older patients were less likely to continue treatment, such that by 150 days, 99 patients (40%) aged 65 years and older and 68 younger patients (25%) had discontinued chemotherapy (difference, 15%; 95% CI, 7%-23%). Overall, 162 patients (24%) had at least 1 adverse clinical event, with more events among patients treated with vs without adjuvant chemotherapy (mean, 0.39 vs 0.16; difference, 0.23; 95% CI, 0.11-0.36; P < .001). Among patients receiving adjuvant chemotherapy, adjusted rates of late clinical adverse events were lower for patients 75 years and older (mean, 0.28) vs for younger patients (0.35 for ages 18-54 years, 0.52 for ages 55-64 years, and 0.45 for ages 65-74 years; P = .008 for any age effect).

CONCLUSIONS

Among patients with stage III colon cancer who underwent surgical resection and received adjuvant chemotherapy, older patients in the community received less-toxic and shorter chemotherapy regimens, and those treated had fewer adverse events than younger patients.

We compared the metric properties of the University of California, Los Angeles (UCLA) activity scale, the Tegner score, and the Activity Rating Scale for assessment of activity levels in 105 patients undergoing THA (48 women; mean age, 63.4 years) and 100 patients undergoing TKA (61 women; mean age, 66.5 years). We assessed construct validity by correlating these scales with the International Physical Activity Questionnaire and different traditional patient self-reporting outcome measures. Test-retest reliability, feasibility, and floor and ceiling effects also were determined. The UCLA scale showed the strongest correlations with the other measures (r = -0.35 to 0.56 for THA; r = -0.55 to 0.23 for TKA) and was the only scale that discriminated between insufficiently and sufficiently active patients undergoing THA and TKA. The UCLA scale had the best reliability, provided the highest completion rate, and showed no floor effects. It seems to be the most appropriate scale for assessment of physical activity levels in patients undergoing total joint arthroplasty.

METHODS

Level III, diagnostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Objective: To describe detection of severe acute respiratory syndrome (SARS)-coronavirus 2 (CoV-2) in seminal fluid of patients recovering from coronavirus disease 2019 (COVID-19) and to describe the expression profile of angiotensin-converting enzyme 2 (ACE2) and Transmembrane Serine Protease 2 (TMPRSS2) within the testicle.

Design: Observational, cross-sectional study.

Setting: Tertiary referral center.

Patient(s): Thirty-four adult Chinese males diagnosed with COVID-19 through confirmatory quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) from pharyngeal swab samples.

Intervention(s): None.

Main outcome measure(s): Identification of SARS-CoV-2 on qRT-PCR of single ejaculated semen samples. Semen quality was not assessed. Expression patterns of ACE2 and TMPRSS2 in the human testis are explored through previously published single-cell transcriptome datasets.

Result(s): Six patients (19%) demonstrated scrotal discomfort suggestive of viral orchitis around the time of COVID-19 confirmation. Severe acute respiratory syndrome-CoV-2 was not detected in semen after a median of 31 days (interquartile range, 29-36 days) from COVID-19 diagnosis. Single-cell transcriptome analysis demonstrates sparse expression of ACE2 and TMPRSS2, with almost no overlapping gene expression.

Conclusion(s): Severe acute respiratory syndrome-CoV-2 was not detected in the semen of patients recovering from COVID-19 1 month after COVID-19 diagnosis. Angiotensin-converting enzyme 2-mediated viral entry of SARS-CoV-2 into target host cells is unlikely to occur within the human testicle based on ACE2 and TMPRSS2 expression. The long-term effects of SARS-CoV-2 on male reproductive function remain unknown.

No hay evidencia de síndrome respiratorio agudo severo - coronavirus 2 en semen de varones que se recuperan de la enfermedad del coronavirus 2019

Objetivo: Describir la detección del síndrome respiratorio agudo severo (SRAS) –coronavirus 2 (CoV-2) en el líquido seminal de pacientes en recuperación de la enfermedad por coronavirus 2019 (COVID-19) y describir el perfil de expresión de la enzima convertidora de angiotensina 2 (ACE2) y Serina Proteasa Transmembrana 2 (TMPRSS2) dentro del testículo.

Diseño experimental: Estudio observacional, transversal.

Lugar de realización: Centro de referencia terciario.

Pacientes: Treinta y cuatro varones chinos adultos diagnosticados con COVID-19 mediante la confirmación cuantitativa de la reacción en cadena de la polimerasa con transcriptasa reversa (qRT-PCR) de muestras de hisopado faríngeo.

Intervenciones: Ninguna.

Principal variable de medida: Identificación de SARS-CoV-2 a través de qRT-PCR de muestras de semen eyaculadas individuales. La calidad del semen no fue evaluada. Los patrones de expresión de ACE2 y TMPRSS2 en los testículos humanos se exploran a través de conjunto de datos de transcriptoma de célula única publicados previamente.

Resultados: Seis pacientes (19%) demostraron molestias escrotales relacionadas con la orquitis viral en el momento de la confirmación de COVID-19. El síndrome respiratorio agudo severo - CoV-2 no se detectó en semen después de una mediana de 31 días (rango intercuartil, 29-36 días) desde el diagnóstico de COVID-19. El análisis de transcriptoma de célula única demuestra una expresión escasa de ACE2 y TMPRSS2, casi sin expresión de genes superpuestos.

Conclusión: El síndrome respiratorio agudo severo-CoV-2 no se detectó en el semen de pacientes que se recuperaron de COVID-19 1 mes después del diagnóstico. La entrada viral mediada por la enzima convertidora de angiotensina 2 del SARS-CoV-2 en las células huésped diana es poco probable que ocurra dentro del testículo humano basado en la expresión de ACE2 y TMPRSS2. Los efectos a largo plazo del SARS-CoV-2 en la función reproductora masculina sigue siendo desconocida.

Keywords: COVID-19; angiotensin-converting enzyme 2; coronavirus; infertility; male; semen.

BACKGROUND

Since the 1970s, incidence rates of esophageal and gastric cardia adenocarcinoma have risen substantially. Reasons for the increasing trends are not well understood.

METHODS

A population-based, case-control study that included esophageal adenocarcinomas (n = 222), gastric cardia adenocarcinomas (n = 277), distal gastric adenocarcinomas (n = 443), and 1356 controls was conducted in Los Angeles County. Unconditional logistic regression was used to calculate odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the 3 tumor types.

RESULTS

After adjustment for demographic factors, smoking, and body size, both hiatal hernia and reflux symptoms emerged as significant independent risk factors. Risk of esophageal adenocarcinoma was increased 3-fold (adjusted OR, 3.61; 95% CI, 2.49-5.25) among those who had reflux symptoms but did not have hiatal hernia, 6-fold (adjusted OR, 5.85; 95% CI, 3.18-10.75) among those who had hiatal hernia but did not have reflux symptoms, and 8-fold (adjusted OR, 8.11; 95% CI, 4.75-13.87) among those who had both reflux symptoms and hiatal hernia. A similar risk pattern was found in relation to history of hiatal hernia and other reflux conditions. A more modest but still significant risk pattern was observed for gastric cardia adenocarcinoma. Among control subjects, there was a significant and positive association between increasing body mass index and history of hiatal hernia and/or reflux symptoms.

CONCLUSIONS

Hiatal hernia, in combination with other reflux conditions and symptoms, was associated strongly with the risk of esophageal adenocarcinoma. These associations were more modest for gastric cardia adenocarcinomas. A significant and positive association between body size and history of hiatal hernia/reflux symptoms also was observed.

Learning in shape identification led to global changes in activation across the entire visual pathway, as revealed with whole-brain fMRI. Following extensive training in a shape identification task, brain activity associated with trained shapes relative to the untrained shapes showed: (1) an increased level of activity in retinotopic cortex (RC), (2) a decrease in activation of the lateral occipital cortex (LO), and (3) a decrease in the dorsal attentional network. In addition, RC activations became more correlated (and LO activation, less correlated) with performance. When comparing target-present and target-absent trials within the trained condition, we observed a similar decrease in the dorsal attentional network but not in the visual cortices. These findings indicate a large-scale reorganization of activity in the visual pathway as a result of learning, with the RC becoming more involved (and the LO, less involved) and that these changes are triggered in a top-down manner depending on the perceptual task performed.

Hispanics are heterogeneous in national origin, evidenced by wide ranges of alcohol abuse and dependence rates across different Hispanic national groups. This paper examines associations between 12-month rates of DSM-IV alcohol abuse and dependence with birthplace and acculturation. The 2006 Hispanic Americans Baseline Alcohol Survey, using a multistage cluster sample design, interviewed 5224 adults (18+ years) in five selected U.S. metropolitan areas: Miami, New York, Philadelphia, Houston, and Los Angeles. Comprehensive data on drinking behavior were collected and the analyses include bivariate and multivariate regression techniques. Alcohol abuse and dependence rates were higher among U.S.-born Puerto Ricans and South/Central Americans compared to their foreign-born counterparts, while no such differences were found for Cuban and Mexican Americans. Overall, those with higher acculturation report higher rates of abuse and dependence (statistically significant only for abuse among Puerto Ricans). Risk factors for abuse include being male and being in the high acculturation group. Risk factors for dependence include being male, being Puerto Rican or Mexican American, having less than a college education, and being U.S.-born. Hispanics were found to share several common risk factors with the larger U.S. population for abuse and dependence, such as male gender, lower education, and lower income.