Frailty-Related Factors among Women Living with and without HIV Aged 40 Years and Older. The Women's Interagency HIV Study.

BACKGROUND: Frailty is a clinical, geriatric syndrome linked to disability and mortality; and may be associated with a variety of factors among underrepresented and underserved women living with HIV (WLWH) and without HIV (WLWOH) transitioning through the adult life course. OBJECTIVES: Determine whether a published set of factors associated cross-sectionally with frailty in WLWH and similar WLWOH at average age 39 years in 2005/2006 were associated with frailty in 2018/2019 among women who initiated frailty assessments at age ≥40 years, or whether a new set of factors were associated with frailty. DESIGN: Cross-sectional analyses within a longitudinal cohort study. SETTING: The multi-center Women's Interagency HIV Study (WIHS). PARTICIPANTS: 1285 participants (951 WLWH, 334 WLWOH), median age 53 years (interquartile range 47-58 years). MEASUREMENTS: The Fried Frailty Phenotype (FFP) in association with 23 factors representing HIV serostatus, other infections, sociodemographic factors, health behaviors, and chronic diseases. RESULTS: Frailty prevalence was 11.1% in 2018/2019 (12.6% among WLWOH, 9.6% among WLWH, p=0.121). The published 2005/2006 final multivariable stepwise regression model contained 9 predictors of frailty. When refit to women in 2018/2019, only age ≥50 years and annual income ≤$12,000 were independently positively associated with frailty; other significant 2005/2006 factors, HIV serostatus, CD4+ count <500 cells/mL among WLWH, smoking, drinking, FIB-4 and eGFR, were not. A newly-derived stepwise model considering all 23 predictors measured in 2018/2019, showed independent positive associations between frailty and age ≥50 years, annual income ≤$12,000, obesity (body mass index (BMI) ≥30kg/m2), and history of tuberculosis and cancer. CONCLUSION: Different chronic and infectious disease factors were associated with frailty among WLWH and WLWOH over the adult life course. Understanding factors associated with frailty by adult life stage, allows identification and implementation of novel, temporal interventions to alleviate frailty-associated outcomes and enhance quality of life among WLWH and WLWOH.

A proteome-integrated, carbon source dependent genetic regulatory network in Saccharomyces cerevisiae.

Integrated regulatory networks can be powerful tools to examine and test properties of cellular systems, such as modelling environmental effects on the molecular bioeconomy, where protein levels are altered in response to changes in growth conditions. Although extensive regulatory pathways and protein interaction data sets exist which represent such networks, few have formally considered quantitative proteomics data to validate and extend them. We generate and consider such data here using a label-free proteomics strategy to quantify alterations in protein abundance for S. cerevisiae when grown on minimal media using glucose, galactose, maltose and trehalose as sole carbon sources. Using a high quality-controlled subset of proteins observed to be differentially abundant, we constructed a proteome-informed network, comprising 1850 transcription factor interactions and 37 chaperone interactions, which defines the major changes in the cellular proteome when growing under different carbon sources. Analysis of the differentially abundant proteins involved in the regulatory network pointed to their significant roles in specific metabolic pathways and function, including glucose homeostasis, amino acid biosynthesis, and carbohydrate metabolic process. We noted strong statistical enrichment in the differentially abundant proteome of targets of known transcription factors associated with stress responses and altered carbon metabolism. This shows how such integrated analysis can lend further experimental support to annotated regulatory interactions, since the proteomic changes capture both magnitude and direction of gene expression change at the level of the affected proteins. Overall this study highlights the power of quantitative proteomics to help define regulatory systems pertinent to environmental conditions.

Frailty and Constellations of Factors in Aging HIV-infected and Uninfected Women--The Women's Interagency HIV Study.

BACKGROUND: Biological similarities are noted between aging and HIV infection. Middle-aged adults with HIV infection may present as elderly due to accelerated aging or having more severe aging phenotypes occurring at younger ages. OBJECTIVES: We explored age-adjusted prevalence of frailty, a geriatric condition, among HIV+ and at risk HIV- women. DESIGN: Cross-sectional. SETTING: The Women's Interagency HIV Study (WIHS). PARTICIPANTS: 2028 middle-aged (average age 39 years) female participants (1449 HIV+; 579 HIV-). MEASUREMENTS: The Fried Frailty Index (FFI), HIV status variables, and constellations of variables representing Demographic/health behaviors and Aging-related chronic diseases. Associations between the FFI and other variables were estimated, followed by stepwise regression models. RESULTS: Overall frailty prevalence was 15.2% (HIV+, 17%; HIV-, 10%). A multivariable model suggested that HIV infection with CD4 count<200; age>40 years; current or former smoking; income ≤$12,000; moderate vs low fibrinogen-4 (FIB-4) levels; and moderate vs high estimated glomerular filtration rate (eGFR) were positively associated with frailty. Low or moderate drinking was protective. CONCLUSIONS: Frailty is a multidimensional aging phenotype observed in mid-life among women with HIV infection. Prevalence of frailty in this sample of HIV-infected women exceeds that for usual elderly populations. This highlights the need for geriatricians and gerontologists to interact with younger 'at risk' populations, and assists in the formulation of best recommendations for frailty interventions to prevent early aging, excess morbidities and early death.

Mean platelet volume is decreased in HIV-infected women.

OBJECTIVES: HIV infection is associated with higher than expected cardiovascular event rates and lowered platelet counts. These conditions are associated with an elevation of mean platelet volume (MPV). The present study compared MPV in HIV-infected and uninfected women and identified factors influencing MPV values in HIV-infected women. METHODS: A total of 234 HIV-infected and 134 HIV-uninfected participants from the Women's Interagency HIV Study (WIHS) had MPV values obtained. HIV-infected women were older, were more likely to have diabetes and had higher triglyceride levels than HIV-uninfected women. RESULTS: The mean platelet count was lower in HIV-infected vs. uninfected women [249 cells/µL (95% confidence interval (CI) 238, 259 cells/µL) vs. 276 cells/µL (95% CI 265, 287 cells/µL), respectively; P < 0.01]. Adjusted mean MPV values were lower in the HIV-infected than in the uninfected group [8.66 fL (95% CI 8.52, 8.79 fL) vs. 9.05 fL (95% CI 8.87, 9.24 fL), respectively]. In multiple regression analysis, after adjusting for other covariates, MPV was positively associated with platelet count, and negatively with HIV infection (model R² = 0.20; P < 0.01). In multiple regression analysis confined to HIV-infected women, a lower MPV was independently associated with a history of AIDS-defining illness (R² = 0.28; P = 0.03), but not with nadir CD4 count or highly active antiretroviral therapy (HAART) use. CONCLUSIONS: HIV-infected women had lower MPV values than uninfected women, suggesting impaired production rather than increased destruction. Higher than expected cardiovascular event rates cannot be attributed to greater platelet reactivity as measured by MPV.

Osteopathia striata congenita with cranial sclerosis and intellectual disability due to contiguous gene deletions involving the WTX locus.

Osteopathia striata congenita with cranial sclerosis (OSCS) is a skeletal dysplasia caused by germline deletions of or truncating point mutations in the X-linked gene WTX (FAM123B, AMER1). Females present with longitudinal striations of sclerotic bone along the long axis of long bones and cranial sclerosis, with a high prevalence of cleft palate and hearing loss. Intellectual disability or neurodevelopmental delay is not observed in females with point mutations in WTX leading to OSCS. One female has been described with a deletion spanning multiple neighbouring genes suggesting that deletion of some neighbouring loci may result in abnormal neurodevelopment. In this cohort of 13 females with OSCS resulting from deletions of WTX, a relationship is observed where deletion of ARHGEF9 and/or MTMR8 in conjunction with WTX results in an additional neurodevelopmental phenotype whereas deletion of ASB12 along with WTX is associated with a good neurodevelopmental prognosis.

Peripheral arterial disease in HIV-infected and uninfected women.

OBJECTIVE: Although HIV infection has been associated with increased risk of subclinical atherosclerosis and cardiovascular events, peripheral arterial disease (PAD) has not been assessed in HIV-infected patients. The objective of this study was to determine the prevalence of, and risk factors for, PAD using ankle-brachial index (ABI) measurement in HIV-infected and uninfected women. METHODS: ABI was determined for 335 participants in the Women's Interagency HIV Study (WIHS). A cross-sectional analysis was conducted to determine factors associated with high (>or=1.40) ABI. RESULTS: The prevalence of low ABI (or=1.40) was 6.9% (n=23). The prevalence of low ABI was too low to allow risk factor analysis. On multivariate analysis, factors associated with high ABI were current cigarette smoking [adjusted odds ratio (OR(adj)) 2.53, 95% confidence interval (CI) 0.99-6.43], being underweight (OR(adj) 11.0, 95% CI 1.61-75.63) and being overweight (OR(adj) 5.40, 95% CI 1.13-25.89). CONCLUSIONS: Although the prevalence of ABI or=1.40 was unexpectedly high. Further studies are indicated to determine the clinical significance of high ABI and its relation to the risk of cardiovascular events in HIV-infected women.

Cortical excitability and age-related volumetric MRI changes.

OBJECTIVE: Normative data on transcranial magnetic stimulation (TMS)-derived measures of cortical excitability in the elderly is sparse. Nevertheless, elderly subjects are included as controls in studies utilizing TMS to investigate disease states. Age-associated increased ventricular cerebrospinal fluid CSF (vCSF) and white matter hyperintensity (WMH) MRI volumes have uncertain significance in non-demented elderly. Information regarding cortical excitability in neurologically intact elderly would augment our understanding of the pathophysiology of aging and assist in the interpretation of TMS studies involving elderly subjects. METHODS: Twenty-four healthy elderly subjects underwent TMS testing to determine outcomes of resting motor threshold (RMT) cortical silent period (cSP) and central motor conduction time for examination in relation to WMH, vCSF, and CNS volumes. RESULTS: Increased vCSF and WMH volumes were associated with decreased right and left hemisphere RMT. Smaller CNS volumes were associated with decreased right hemisphere RMT and shorted cSP. CONCLUSIONS: Commonly observed age-associated MRI changes are associated with findings consistent with increased cortical excitability. SIGNIFICANCE: Age-related MRI findings likely reflect changes at a cellular level, and may influence cognitive and motor integrity in the elderly. Future TMS studies investigating cortical excitability may wish to consider neuroimaging markers of neurodegeneration prior to enrolling elderly subjects as controls.

Function of a genetically modified human liver cell line that stores, processes and secretes insulin.

An alternative approach to the treatment of type I diabetes is the use of genetically altered neoplastic liver cells to synthesize, store and secrete insulin. To try and achieve this goal we modified a human liver cell line, HUH7, by transfecting it with human insulin cDNA under the control of the cytomegalovirus promoter. The HUH7-ins cells created were able to synthesize insulin in a similar manner to that which occurs in pancreatic beta cells. They secreted insulin in a regulated manner in response to glucose, calcium and theophylline, the dose-response curve for glucose being near-physiological. Perifusion studies showed that secretion was rapid and tightly controlled. Removal of calcium resulted in loss of glucose stimulation while addition of brefeldin A resulted in a 30% diminution of effect, indicating that constitutive release of insulin occurred to a small extent. Insulin was stored in granules within the cytoplasm. When transplanted into diabetic immunoincompetent mice, the cells synthesized, processed, stored and secreted diarginyl insulin in a rapid regulated manner in response to glucose. Constitutive release of insulin also occurred and was greater than regulated secretion. Blood glucose levels of the mice were normalized but ultimately became subnormal due to continued proliferation of cells. Examination of the HUH7-ins cells as well as the parent cell line for beta cell transcription factors showed the presence of NeuroD but not PDX-1. PC1 and PC2 were also present in both cell types. Thus, the parent HUH7 cell line possessed a number of endocrine pancreatic features that reflect the common endodermal ancestry of liver and pancreas, perhaps as a result of ontogenetic regression of the neoplastic liver cell from which the line was derived. Introduction of the insulin gene under the control of the CMV promoter induced changes in these cells to make them function to some extent like pancreatic beta cells. Our results support the view that neoplastic liver cells can be induced to become substitute pancreatic beta cells and become a therapy for the treatment of type I diabetes.

Epidemiology and natural history of ligase chain reaction detected chlamydial and gonococcal infections.

OBJECTIVES: Ligase chain reaction (LCR) technology has dramatically increased the sensitivity of tests for sexually transmitted infections (STIs). It is unknown whether low copy infections (LCR positive, culture negative) have any clinical consequences. We assessed the clinical significance of untreated low copy Chlamydia trachomatis and Neisseria gonorrhoeae infections in a cohort of sexually active women. METHODS: We studied a cohort of sexually active women followed at 6 month intervals for up to 3 years. Frozen urine specimens from 181 women with negative cultures for C. trachomatis and N. gonorrhoeae who were 'high risk' (defined as being less than 40 years old at baseline, and having either Trichomonas vaginalis at baseline or a history of more than one sexual partner during the 12 months before baseline) were tested for C. trachomatis and N. gonorrhoeae by LCR (Abbott Laboratories, Abbott Park, IL, USA). The specimens from all visits for each person were pooled and LCR was performed on the pool. Laboratory results were linked to clinical information. We also tested all urine samples obtained from patients with a positive culture. RESULTS: 10 additional infections (nine C. trachomatis and one N. gonorrhoeae) were detected with LCR technique. None of the women with low copy infection had evidence of subsequent pelvic inflammatory disease or ectopic pregnancy. Pooling of urine samples resulted in a 47% decline in the number of tests performed. CONCLUSIONS: Additional STIs can be identified when using LCR. Pooling of urine specimens is a cost saving technique for C. trachomatis and N. gonorrhoeae testing.

A case-control study of beliefs and behaviors associated with sexually transmitted disease occurrence in Estonia.

BACKGROUND: Epidemiologic data document rapidly increasing sexually transmitted disease (STD) rates throughout Eastern Europe. GOAL: This case-control study was designed to delineate factors contributing to the STD epidemic in Estonia. STUDY DESIGN: For this study, 189 study participants and 112 control subjects completed a behavioral questionnaire and underwent testing for Neisseria gonorrhoeae, Chlamydia trachomatis, and Treponema pallidum. RESULTS: The prevalence of STDs among the control subjects was 32%. Although the participants believed that condoms prevent STDs, only 17% reported consistent use. Methods believed to prevent transmission included washing the genitals (65%), urinating (26%), douching (35%), and using oral contraceptives (19%). An interaction between sex and travel outside Estonia (odds ratio, 0.1; 95% CI, 0-0.7) reflects the fact that males with STDs were more likely to report travel (46% of participants and 45.5% of control subjects with STD) than were those without STD (16.1% of controls without STD). CONCLUSIONS: STD rates are related to high-risk sexual behavior among males traveling outside of Estonia. Intervention is needed to promote understanding of disease transmission dynamics in this area, and to decrease sexual risk behavior, particularly in the context of travel.

Retention of women enrolled in a prospective study of human immunodeficiency virus infection: impact of race, unstable housing, and use of human immunodeficiency virus therapy.

Even though women and people of color represent an increasing proportion of US acquired immunodeficiency syndrome (AIDS) cases, few research studies include adequate representation of these populations. Here the authors describe recruitment and retention of a diverse group of human immunodeficiency virus (HIV)-infected and at risk HIV-uninfected women in a prospective study operating in six sites across the United States. Methods used to minimize loss to follow-up in this cohort are also described. For the first 10 study visits that occurred during a 5-year period between 1994 and 1999, the retention rate of participants was approximately 82%. In adjusted Cox analysis, factors associated with retention among all women were older age, African-American race, stable housing, HIV-infected serostatus, past experience in studies of HIV/AIDS, and site of enrollment. In an adjusted Cox analysis of HIV-infected women, African-American race, past experience in studies of HIV/AIDS, site of enrollment, and reported use of combination or highly active antiretroviral HIV therapy at the last visit were significantly associated with retention. In adjusted Cox analysis of HIV-uninfected study participants, only the site of enrollment was significantly associated with study retention. These results show that women with and at risk for HIV infection, especially African-American women, can be successfully recruited and retained in prospective studies.

What constitutes an effective but safe initial dose of lidocaine to test a thoracic epidural catheter?

To investigate the effects of age and dose on the spread of thoracic epidural anesthesia, we placed thoracic epidural catheters in 50 surgical patients divided into groups by age (Group I [young], 18-51 yr; Group II [old], 56-80 yr) and randomly assigned patients to receive either 5 mL (A) or 9 mL (B) of 2% lidocaine (plain) injected via the epidural catheter. Hemodynamic variables were measured (heart rate, mean arterial blood pressure, noninvasive impedance cardiac index) at baseline and every 5 min for 30 min. Detectable blockade occurred within 8 min after injection of 3 + 2 mL or 3 + 6 mL in 48 of 50 patients. Maximum spread of analgesia to pinprick occurred 15-23 min after completion of local anesthetic injection and was significantly different between age and volume groups by two-way analysis of variance (Group IA [young 5], 10.9 +/- 4.0 dermatomes; Group IIB [young 9], 13.9 +/- 4.5 dermatomes; Group IIA [old 5], 14.1 +/- 5.6 dermatomes; and Group IIB [old 9], 17.4 +/- 5.1 dermatomes). Minor decreases in mean arterial blood pressure (8%-17%) and heart rate (4%-11%) were noted. Two patients in the Old 9 group required IV ephedrine or ephedrine/atropine to treat hypotension and bradycardia. We conclude that given the rapid onset (3-8 min), extensive spread (11-14 dermatomal segments), and consistent hemodynamic stability, thoracic epidural anesthesia should be initiated with lidocaine 100 mg (5 mL 2% lidocaine) to establish proper location of the catheter in the epidural space in both younger and older patients.

Prevalence and predictors of skin disease in the Women's Interagency HIV Study (WIHS).

OBJECTIVE: We attempted to determine the prevalence and predictors of skin disease in a cohort of women with and at risk for HIV infection. METHODS: We analyzed baseline data from a multicenter longitudinal study of HIV infection in women. RESULTS: A total of 2018 HIV-infected women and 557 HIV-uninfected women were included in this analysis. Skin abnormalities were reported more frequently among HIV-infected than uninfected women (63% vs 44%, respectively; odds ratio [OR] 2.10; 95% confidence interval [95% CI], 1.74-2.54). Infected women were also more likely to have more than 2 skin diagnoses (OR, 3.27; 95% CI, 1.31-8.16). Folliculitis, seborrheic dermatitis, herpes zoster, and onychomycosis were more common among HIV-infected women (P < .05). Independent predictors of abnormal findings on skin examination in the infected women were African American race (OR, 1.38; 95% CI, 1.07-1.77), injection drug use (OR, 2.74; 95% CI, 2.11-3.57), CD4(+) count less than 50 (OR, 1.68; 95% CI, 1.17-2.42), and high viral loads (100,000-499,999 = OR, 1.77; 95% CI, 1.32-2.37; > 499,999 = OR, 2.15; 95% CI, 1.42-3.27). CONCLUSION: HIV infection was associated with a greater number of skin abnormalities and with specific dermatologic diagnoses. Skin abnormalities were also more common among women with CD4(+) cell depletion or higher viral load.

Postnatal cell proliferation and death in a lateralized, gender-related, asymmetric nucleus.

Sexual differentiation and lateralization of neurone number in a discrete forebrain nucleus (SDApc) related to masculine vocal emission, occur contemporaneously in postnatal (P0-P15) gerbils. Stereological estimates of cell proliferation and death during SDApc organization were made by BrdU labelling and pyknosis, respectively. Results confirmed that rates of apoptosis were greater in females and lateralized in males. Immunoreactive BrdU cells, located in the SDApc at P0-P6, with low levels at P15, were not numerically different between the sexes. Only at one age, P0, in males, was a left-right difference seen in BrdU-immunoreactive cell numbers. Microglia, identified by isolectin immunostaining, were numerically similar to BrdU cells. We suggest that apoptosis, rather than neurogenesis, differentiates and lateralizes SDApc organization, and proliferating cells are microglia, phagocytosing debris.

Aneuploidy screening in direct chorionic villus samples by fluorescence in situ hybridisation: the use of commercial probes in a clinical setting.

The results of screening for the common aneuploidies involving chromosomes 13, 18, 21, X and Y by florescent in-situ hybridisation (FISH) in direct preparations from 100 chorionic villus samples from pregnancies between 10 and 20 weeks' gestation are reported. Samples prepared using routine methods and analysed with commercially available probes, accurately detected 12 cases of fetal aneuploidy, all referred because of developmental abnormality. Three of the four cases where chromosome abnormality was detected in cultured villi but not by the direct fluorescence in situ hybridisation (FISH) assay, were due to confined placental mosaicism. No chromosomal anomalies were found in the 20 low risk cases where the referral reason was a familial single gene disorder. We conclude that the FISH assay with commercial probes may act as an accurate and less labour intensive alternative to direct chromosome analysis of chorionic villus samples. In cytogenetically low risk cases its use can obtain a result within the time needed for DNA analysis and avoid the need to set up cultures.

Status of methods for assessing bacterial cell surface charge properties based on zeta potential measurements.

Surface interfacial physiology is particularly important to unicellular organisms with regard to maintenance of optimal cell function. Bacterial cell surfaces possess net negative electrostatic charge by virtue of ionized phosphoryl and carboxylate substituents on outer cell envelope macromolecules which are exposed to the extracellular environment. The degree of peripheral electronegativity influences overall cell surface polarity and can be assessed on the basis of zeta potential which is most often determined by estimating the electrophoretic mobility of cells in an electric field. The purpose of this review is to provide bacteriologists with assistance as they seek to better understand available instrumentation and fundamental principles concerning the estimation of zeta potential as it relates to bacterial surface physiology.

UVA-induced oxidative damage in retinal pigment epithelial cells after H2O2 or sparfloxacin exposure.

Retinal impairment is one of the leading causes of visual loss in an aging human population. To explore a possible cause for retinal damage in the human population, we have monitored DNA oxidation in human retinal pigment epithelial (RPE) cells after exposure to hydrogen peroxide (H2O2) or the quinolone antibacterial sparfloxacin. When H2O2- or sparfloxacin-exposed cells were further exposed to ultraviolet A (UVA) irradiation, oxidative damage to the DNA of these cells was greatly increased over baseline values. This RPE+pharmaceutical-UVA cell system was developed to mimic in vivo retinal degeneration, seen in mouse studies using quinolone and UVA exposure. DNA damage produced by sparfloxacin and UVA in RPE cells could be remedied by the use of antioxidants, indicating a possible in vivo method for prevention or minimization of retinal damage in humans

Domestic violence and childhood sexual abuse in HIV-infected women and women at risk for HIV.

OBJECTIVES: The purpose of this study was to determine the prevalence and effect of domestic violence and childhood sexual abuse in women with HIV or at risk for HIV infection. METHODS: Participants with HIV or at risk for HIV infection enrolled in the Women's Interagency HIV Study. Childhood sexual abuse; all physical, sexual, and coercive violence by a partner; HIV serostatus; demographic data; and substance use and sexual habits were assessed. RESULTS: The lifetime prevalence of domestic violence was 66% and 67%, respectively, in 1288 women with HIV and 357 uninfected women. One quarter of the women reported recent abuse, and 31% of the HIV-seropositive women and 27% of the HIV-seronegative women reported childhood sexual abuse. Childhood sexual abuse was strongly associated with a lifetime history of domestic violence and high-risk behaviors, including using drugs, having more than 10 male sexual partners and having male partners at risk for HIV infection, and exchanging sex for drugs, money, or shelter. CONCLUSIONS: Our data support the hypothesis of a continuum of risk, with early childhood abuse leading to later domestic violence, which may increase the risk of behaviors leading to HIV infection.

Neuronal cell death during sexual differentiation and lateralisation of vocal communication.

A rodent analogy has been established to investigate the neural mechanisms occurring during sexual differentiation and lateralization. A sexually dimorphic hypothalamic nucleus (SDApc) is closely associated with a stereotyped, courtship vocalisation in male gerbils. Stereological analysis of SDApc cytoarchitecture reveals that neuron number and nuclear volume are asymmetric in male adults. Strikingly, neuron number on the left side of the SDApc correlates significantly with the rate of the courtship call in males. Exogenous testosterone treatment in female neonates masculinises and lateralises SDApc structure and function. Neuronal programmed cell death (apoptosis), manifested in SDApcs of neonates, is more frequent in females. Significantly, apoptosis in males is lateralised, as revealed by lateral asymmetry of neuron number at postnatal day 16. It is concluded that neuroendocrine-dependent, sexual differentiation and lateralization are concurrent and influenced by apoptotic mechanisms. It is suggested that apoptosis is the result of a genetically-driven device, inherent in postmitotic, undifferentiated cells which may have recently migrated into the SDApc. The genomic mechanism inducing lateralised apoptosis is apparently activated only neonatally in males.

Laterally asymmetrical cell number in a sexually dimorphic nucleus in the gerbil hypothalamus is correlated with vocal emission rates.

A lateralized relationship between the total volume of a discrete area in a hypothalamic, sexually differentiated nucleus (SDApc) and stereotyped vocalization exists in male Mongolian gerbils. In this present study, using unbiased stereological methods, two cytoarchitectural estimates of the SDApc's structure, neuron number, and nuclear volume were found to be sexually differentiated and also laterally asymmetrical in adult males. In ovariectomized females receiving exogenous testosterone, no cytoarchitectural component was asymmetrical. Significantly, the estimate of neuron number, but not nuclear volume, in the left SDApc of males was correlated with vocal emission rate. The authors conclude that a specific, sex-related cytoarchitectural SDApc parameter shows left-right asymmetry, suggesting the SDApc has an intimate role in mediating hemispheric specialization rather than just being an end point index of individual structural variability.