Development and validation of a prediction model for falls among older people using community-based data.

This is the first study to employ multilevel modeling analysis to develop a predictive tool for falls in individuals who have participated in community group exercise over a year. The tool may benefit healthcare workers in screening community-dwelling older adults with various levels of risks for falls. PURPOSE: The aim of this study was to develop a calculation tool to predict the risk of falls 1 year in the future and to find the cutoff value for detecting a high risk based on a database of individuals who participated in a community-based group exercise. METHODS: We retrospectively reviewed a total of 7726 physical test and Kihon Checklist data from 2381 participants who participated in community-based physical exercise groups. We performed multilevel logistic regression analysis to estimate the odds ratio of falls for each risk factor and used the variance inflation factor to assess collinearity. We determined a cutoff value that effectively distinguishes individuals who are likely to fall within a year based on both sensitivity and specificity. RESULTS: The final model included variables such as age, sex, weight, balance, standing up from a chair without any aid, history of a fall in the previous year, choking, cognitive status, subjective health, and long-term participation. The sensitivity, specificity, and best cutoff value of our tool were 68.4%, 53.8%, and 22%, respectively. CONCLUSION: Using our tool, an individual's risk of falls over the course of a year could be predicted with acceptable sensitivity and specificity. We recommend a cutoff value of 22% for use in identifying high-risk populations. The tool may benefit healthcare workers in screening community-dwelling older adults with various levels of risk for falls and support physicians in planning preventative and follow-up care.

Long-term participation in community-based group resistance exercises delays the transition from robustness to frailty in older adults: a retrospective cohort study.

BACKGROUND: How community-based group resistance exercises affect the transition from robustness to frailty remains unclear. Thus, we conducted a retrospective cohort study to determine whether the trajectory from robustness to frailty over age differed depending on the duration of participation in group exercises. METHODS: We analyzed the Kihon Checklist (KCL) score of community-dwelling elderly residents of Sumoto city, Hyogo prefecture, who participated in community-based group resistance exercises between April 2010 and December 2019. Finally, 2567 older individuals were analyzed using multilevel modeling. The explanatory variables of interest were the frailty score measured using the KCL for each individual, where 0-3, 4-7, and ≥8 points denoted robustness, pre-frailty, and frailty, respectively. We considered age, sex, systolic blood pressure, pulse, duration of participation, and change in KCL score from baseline as possible confounders. Participants were classified as follows based on the duration of participation in the exercises: <3 times, short-term participation group; 4-6 times; mid-term participation group; and 7-13 times, long-term participation group. The mean duration from the baseline physical test for the total sample was 2.35 years (SD=2.51). RESULTS: The participants' mean total KCL score at baseline was 4.9±3.7. Multilevel modeling analysis revealed that the KCL scores changed by 0.82 points for each additional year of age (p<0.001) and changed by - 0.93 points for long-term participate group (p<0.001). The Estimated Marginal Means (EMM) of the KCL score was 3.98 (95%CI: 3.69, 4.28) points in the short-term participation group and was significantly worse than that of the long-term participation group at 70 years of age (p=0.001). The EMM was 4.49 (95%CI: 4.24, 4.74) at 75 years of age in the mid-term participation group and was significantly worse than that of the long-term participation group. The EMM was 3.87 (95%CI: 3.57, 4.16) in the long-term participation group and significantly better than that of the short-term (p<0.001) and mid-term (p=0.002) participation groups. CONCLUSION: Participation in community-based group resistance exercises prolongs the transition from robustness to frailty. The improved KCL scores at baseline in the long-term participation group remained in the robust range at 75 years of age, which suggests the importance of initiating participation before the onset of functional decline.

Assessing timewise changes over 15 months in life-space mobility among community-dwelling elderly persons.

BACKGROUND: The purpose of this study was to examine the differences of timewise changes in life-space mobility between elderly people living alone and those living with others among community-dwelling elderly people from a day care facility with a rehabilitation service for seniors. METHODS: The present study used a longitudinal design with repeated measures every 3 months. In conformity with our inclusion criteria, this study included 233 community-dwelling elderly users of a day care facility with rehabilitation services for seniors in Japan. We analyzed the life-space assessment (LSA) scores collected at five time points (baseline, 3 months, 6 months, 9 months, and 12 months) using mixed-effects models with random intercepts and slopes over time. In the present study, the explanatory variables of interest were time, and living situation (living alone or with others). As possible confounders, we considered the following: (a) age, (b) sex, (c) social frailty, (d) physical frailty, (e) mild cognitive impairment (MCI), (f) depression, and (g) economic satisfaction. RESULTS: The mean age of participants was 78.9 years (SD = 7.7), their mean LSA score was 60.1 points (SD = 25.7), and 42.9% of the participants were men. After adjusting for age, gender, frailty, depression, MCI, and economic satisfaction, the mean LSA score of older adults who lived with others was significantly lower (7.42 points, 95%CI = - 18.30 to - 0.15, p = 0.048) than that older adults who lived alone. DISCUSSION: Community-dwelling older adults who used a day care center with rehabilitation services and lived with others had a smaller life-space at baseline than those who lived alone. This suggests that there is a need to pay more attention to social frailty among both older adults who live alone and those who live with others. CONCLUSIONS: According to a multilevel analysis growth model, elderly persons who lived with others had significantly lower life-space mobility than those who lived alone.

Transmitochondrial mice as models for primary prevention of diseases caused by mutation in the tRNA(Lys) gene.

We generated transmitochondrial mice (mito-mice) that carry a mutation in the tRNA(Lys) gene encoded by mtDNA for use in studies of its pathogenesis and transmission profiles. Because patients with mitochondrial diseases frequently carry mutations in the mitochondrial tRNA(Lys) and tRNA(Leu(UUR)) genes, we focused our efforts on identifying somatic mutations of these genes in mouse lung carcinoma P29 cells. Of the 43 clones of PCR products including the tRNA(Lys) or tRNA(Leu(UUR)) genes in mtDNA of P29 cells, one had a potentially pathogenic mutation (G7731A) in the tRNA(Lys) gene. P29 subclones with predominant amounts of G7731A mtDNA expressed respiration defects, thus suggesting the pathogenicity of this mutation. We then transferred G7731A mtDNA into mouse ES cells and obtained F0 chimeric mice. Mating these F0 mice with C57BL/6J (B6) male mice resulted in the generation of F1 mice with G7731A mtDNA, named "mito-mice-tRNA(Lys7731)." Maternal inheritance and random segregation of G7731A mtDNA occurred in subsequent generations. Mito-mice-tRNA(Lys7731) with high proportions of G7731A mtDNA exclusively expressed respiration defects and disease-related phenotypes and therefore are potential models for mitochondrial diseases due to mutations in the mitochondrial tRNA(Lys) gene. Moreover, the proportion of mutated mtDNA varied markedly among the pups born to each dam, suggesting that selecting oocytes with high proportions of normal mtDNA from affected mothers with tRNA(Lys)-based mitochondrial diseases may be effective as a primary prevention for obtaining unaffected children.

A somatic T15091C mutation in the Cytb gene of mouse mitochondrial DNA dominantly induces respiration defects.

Our previous studies provided evidence that mammalian mitochondrial DNA (mtDNA) mutations that cause mitochondrial respiration defects behave in a recessive manner, because the induction of respiration defects could be prevented with the help of a small proportion (10%-20%) of mtDNA without the mutations. However, subsequent studies found the induction of respiration defects by the accelerated accumulation of a small proportion of mtDNA with various somatic mutations, indicating the presence of mtDNA mutations that behave in a dominant manner. Here, to provide the evidence for the presence of dominant mutations in mtDNA, we used mouse lung carcinoma P29 cells and examined whether some mtDNA molecules possess somatic mutations that dominantly induce respiration defects. Cloning and sequence analysis of 40-48 mtDNA molecules from P29 cells was carried out to screen for somatic mutations in protein-coding genes, because mutations in these genes could dominantly regulate respiration defects by formation of abnormal polypeptides. We found 108 missense mutations existing in one or more of 40-48 mtDNA molecules. Of these missense mutations, a T15091C mutation in the Cytb gene was expected to be pathogenic due to the presence of its orthologous mutation in mtDNA from a patient with cardiomyopathy. After isolation of many subclones from parental P29 cells, we obtained subclones with various proportions of T15091C mtDNA, and showed that the respiration defects were induced in a subclone with only 49% T15091C mtDNA. Because the induction of respiration defects could not be prevented with the help of the remaining 51% mtDNA without the T15091C mutation, the results indicate that the T15091C mutation in mtDNA dominantly induced the respiration defects.

The relationship between twin language, twins' close ties, and social competence.

This study investigated the relationship between twin language, twins' close ties, and social competence in a prospective longitudinal study. We hypothesized that twins whose tie is close would be more likely to develop a twin language, and these twins would be less likely to develop social competence. In addition, we hypothesize that some environmental factors, such as having an older sibling, preschool attendance, zygosity, and sex are also related to twin language, twins' close ties, and social competence. At baseline in 1999 a mailed questionnaire survey was conducted, and a follow-up questionnaire was distributed in 2004 among 958 mothers. As a result, 516 respondents returned the questionnaire (53.9%). In this study, we used 261 twin pairs aged from 6 to 12 years (school-age children) for analysis, excluding those with missing values. In the present study, we found that zygosity and sex were associated with twins' close ties. Having an older sibling and preschool attendance did not affect the twins' close tie, twin language, or social competence. One of the most important findings was that social competence was not affected directly by twins' close tie, but was affected when a twin language was found.

Non-cholera Vibrio infections in Southeast Asia: A systematic review and meta-analysis.

We reviewed and analyzed the existing data on vibriosis in Southeast Asia to better understand its burden and prevalent causal agents. We searched PubMed, Web of Science, and EMBASE for studies published between January 2000 and April 2024. A random-effects meta-analysis was used to estimate the pooled isolation rate of non-cholera Vibrio species. Among the 1385 retrieved studies, 22 met the inclusion criteria for the systematic review and 11 were included in the meta-analysis. The pooled isolation rate of non-cholera Vibrio species among diarrheal patients was 5.0 %. Most species that caused vibriosis included V. parahaemolyticus, V. mimicus, V. vulnificus, non-O1/non-O139 V. cholerae, V. fluvialis, and V. alginolyticus. Pooled isolation rate of V. parahaemolyticus and non-O1 V. cholerae were 7.0, and 4.0, respectively. The prevalence of vibriosis in Southeast Asia is non-negligible. Public health strategies should prioritize enhanced surveillance, and clinicians should consider vibriosis in diarrheal patients with seafood consumption history.

Relationship between Fatigue and Self-Perception of Constipation in Community-Dwelling Older Adults during the COVID-19 Pandemic.

Fatigue and constipation are common symptoms among community-dwelling older adults; however, no studies have explored the relationship between both symptoms in said group. Therefore, this study aimed to examine the relationship between fatigue and self-perception of constipation in community-dwelling older adults during the COVID-19 pandemic. A cross-sectional survey was conducted among 97 older people (response rate: 73.2%) between July and November 2021. Backward−forward stepwise linear regression was performed to identify possible predictors of fatigue among the explanatory variable (self-perception of constipation) and possible confounders, which included (a) age, (b) motor fitness scale, (c) economic satisfaction, (d) subjective memory impairment, (e) subjective health, (f) depression, (g) living alone or not, (h) sex, and (i) frequency of exercise. The intercept of the fatigue score was 42.48 points (95% CI = 32.40 to 49.99, p < 0.001). The results showed that the fatigue score in community-dwelling older adults who had self-perception of constipation was significantly lower (i.e., they had higher fatigue; B = −4.49, 95% CI = −6.58 to −2.40, p < 0.001) compared to those who did not have self-perception of constipation. Therefore, there is a need to develop self-management strategies that older people can use to improve the self-perception of constipation.

Associations between physical function, falls, and the fear of falling among older adults participating in a community-based physical exercise program: A longitudinal multilevel modeling study.

OBJECTIVES: Exercises that target muscle strength, balance, and gait prevent falls in older people. Moreover, exercise may reduce fear of falling by improving physical function. Many studies have examined the risk factors for falls and fear of falling separately. However, few studies have examined the associations between physical function, falls, and fear of falling simultaneously. This study aimed to identify the key physical functions influencing falls and fear of falling. DESIGN: Longitudinal observational study SETTING AND PARTICIPANTS: This study included 2,397 older adults (women: 82.8%, mean age: 74.3 ± 8.0 years) who participated in community-based physical exercise. METHODS: Physical functions such as muscle strength, balance, gait speed, and flexibility were measured regularly during the program. A questionnaire regarding falls and fear of falling was also administered simultaneously. Multilevel modeling was used to investigate the association between physical function and falls and fear of falling. RESULTS: The prevalence of falls and fear of falling at enrolment were 27.1% and 49.8%, respectively. Statistical analyses revealed that (1) falls were significantly associated with balance, age, fall history, fear of falling, and duration of participation; (2) fear of falling was significantly associated with muscle strength, balance, gait speed, age, and fall history. Long-term participation was significantly associated with an improvement in balance. CONCLUSIONS AND IMPLICATIONS: The risk factors for falls and fear of falling were different. Our research showed the importance of including balance training in all prevention programs.

The Differential Heritability of Social Adjustment by Sex.

Sex differences in social adjustment are frequently observed; however, there has been very little research on adaptability in the individual and social domains. The aim of this study was to investigate the sex difference in social abilities, such as high self-appeal, sociability, school adaptation, and home adaptation between school-age males and females. The sample for this study included both same-sex and opposite-sex twin pairs: a total of 467 twin pairs. We classified them into three groups: a group of those in lower classes of elementary school, a group of those in higher classes of elementary school, and a group of those in junior high school. The heritability of school adaptation was estimated to be 95% in males and 54% in females in the junior high school group. The full sex-limitation model showed a better fit in this group, and this means that a qualitative genetic difference exists. For school adaptation, there was no sex difference in lower elementary school classes; however, a quantitative difference appeared in higher classes of elementary school. Moreover, a qualitative difference appeared in junior high school. From this research, it became clear that sex differences in heritability exist for school adaptation, and there was a marked increase from the elementary school children to the junior high school children.

Long-term participation in community group exercise improves lower extremity muscle strength and delays age-related declines in walking speed and physical function in older adults.

BACKGROUND: The effects of group exercise on the physical function of community-dwelling older adults remain unclear. The changes in lower extremity muscle strength, timed up and go (TUG) time, and the motor fitness scale (MFS), over time, among older adults who expressed a willingness to participate in community-based physical exercise groups, were determined using multilevel modelling. METHODS: We analyzed data of 2407 older adults between April 2010 and December 2019 from the registry of physical tests of community-based physical exercise groups. We conducted a retrospective cohort study to assess the effect of physical exercise on lower extremity muscle strength, TUG time, and MFS scores. The durations of the exercises were evaluated by frequency of physical test's participate. RESULTS: A deterioration in lower extremity muscle strength was found in the short-term participant group only. However, in the mid-term and long-term participation groups, lower extremity muscle strength showed a trend of improvement. The TUG time and the MFS score were negatively correlated with increasing age in both groups divided by the duration of participation. However, there was a slower rate of deterioration in the long-term participation group. DISCUSSION: Lower extremity muscle strength, TUG time, and MFS scores decline with increasing age and there were differences in the slope of deterioration that depended on the duration of participation in community-based group exercise. CONCLUSION: Participation in group exercise improved lower extremity muscle strength, TUG time, and MFS scores of older adults living in a community. The positive effects of group exercise were dependent on long-term participation.

[Social development of twins: the need for intervention to avoid adverse effects of twin language].

Social competence is one of the most important accomplishments of human development, and this skill in human relationships is learned through communication. Therefore, it is considered that delays in language development could be a barrier to building human relationships and social competence. Although it is well known that there are delays in language development in twins compared with that of singletons, little is known about how these linguistic delays affect the development of social competence. Because twin language is a language that is unique to each pair of twins and cannot be understood by either their mother or others, it may be assumed that the social competence of twins who have a twin language is less than that of twins who don't have a twin language. Therefore, in this prospective longitudinal study we also investigated the relationship between twin language and social competence. A mailed questionnaire survey was conducted in 958 mothers as a follow-up of a study conducted in 2004. As a result, 522 respondents returned the questionnaire (53.9%). In this study, we used only 256 twins aged 6- 12-years-old (school-age children) for analysis, excluding those with missing values. Multiple logistic regression analysis was employed. In the second child of twins, a low birth weight, the appearance of twin language and gestosis of the mother were positively related with social unbalance (OR = 1.846, 2.022 and 1.903). On the other hand, with the first child, however, there was no such link. The present results indicate that twin language might influence social competence in school-age children. It has been believed that linguistic intervention is unnecessary, because most twin language disappears spontaneously. However, early intervention, for example linguistic assistance by public health nurses or psychologists and early enrollment in a preschool may be necessary for twins with a twin language, to avoid adverse consequences in social competence at school-age.

Relationship between parents' report rate of twin language and factors related to linguistic development: older sibling, nonverbal play and preschool attendance.

The definition and nature of twin language has been a focus of recent studies concerned with the phenomenon. There has been a call for a tighter definition and understanding of the meaning of twin language (Thorpe et al., 2001). This article sought to identify social factors associated with the parent report of twin language and thus provide further understanding of the phenomenon. Data from 583 mothers of twins aged 25 to 59 months were analyzed using multiple logistic regression. Factors included in the modeling of parent-report twin language included social experience factors such as presence of siblings, attendance at preschool education and reports of nonverbal play. It was found that twin pairs who didn't have an older sibling, who showed frequent nonverbal play and who didn't attend preschool were more likely to have a twin language. Moreover, in the group not having an older sibling, the influence of whether twins attended preschool or not was strong and the odds ratio was 0.589 (95% confidence intervals 0.360-0.963). The findings suggest that social experience factors are important predictors of the parent reporting of twin language.

Linguistic features of Japanese twins at 3 or 4 years of age evaluated by Illinois test of psycholinguistic abilities.

In general, twins have delayed language development early in childhood compared with singletons. The purpose of this study was to clarify the overall linguistic features of twins. A Japanese version of the Illinois Test of Psycholinguistic Abilities (ITPA) was administered in 24 twin pairs (aged 3 to 4 years) at their own homes. The overall language abilities of the twins were in the normal range (based on ITPA normative data: mean scale score 36.0 +/- 6.0 points), and for the ITPA subtests only, Auditory Reception fell within the range of language disorder (mean scale score 24.9 +/- 5.1 points). The findings suggest that in 3- to 4-year-old Japanese twins, overall language abilities are not delayed. However, there may be specific difficulties with auditory reception skills.

The Japanese Study of Adult Twins Reared Apart and Growing Old Separately.

More than 100 pairs of adult twins, reared apart and growing old separately, have participated in the Japanese Study of Adult Twins Reared Apart and Growing Old Separately since it began in 1974. The subjects are 161 pairs of adult twins born between 1910 and 1945 in Japan. The main focus of this study is to investigate the influences of environmental factors and life history on life satisfaction and psychological well-being in later adulthood. A mail survey has been conducted on these twins each year since 1974. To date, the Wechsler Adult Intelligent Scale, Maudsley Personality Inventory, Newgarten Life Satisfaction Index, comprehensive medical examinations and personal interviews have been conducted for 12 twin pairs residing in various areas of Japan.

The Osaka University Aged Twin Registry: epigenetics and identical twins discordant for aging-dependent diseases.

The Osaka University Aged Twin Registry (OUATR) is the largest adult twin registry in Japan. Since its establishment in 1974, the OUATR has conducted a number of studies with particular focus on the environmental contribution to physical-cognitive-mental aging, longevity and aging-dependent diseases in later adulthood. The registry consists of 12,000 pairs of Japanese twins born between 1900 and 1935. Two hundred and fifty pairs of twins have undergone comprehensive medical examination to date. Follow-up questionnaires have been mailed out on a regular basis, for the purpose of checking current vital statuses, health conditions, and so forth. The main objective of this longitudinal twin study is to contribute to the prevention of lifestyle-related diseases and the promotion of successful aging.

Association between subjective memory complaints and impaired higher-level functional capacity in people aged 60 years or older.

OBJECTIVE: We aimed to investigate the association between subjective memory complaints and higher-level functional capacity in either people with long-term care needs or those who require help to maintain functional capacity. METHODS: We conducted a cross-sectional study among participants aged 60 years or older. We measured subjective memory complaints, higher-level functional capacity, and depressive symptoms, and then estimated odds ratios (ORs) by multiple logistic analysis. Subjective memory complaints were used as the predictor variable, higher-level functional capacity as the outcome variable, and age, depressive symptoms, medical history of diabetes and hypertension, frequency of going out, falling within a year, and body mass index as possible confounders. We assessed higher-level functional capacity using the Tokyo Metropolitan Institute of Gerontology (TMIG) index of competence score ≤5 as a cut-off (which is associated with higher one-year mortality rates). RESULTS: We conducted analyses using 501 people aged 60 years or older. Among women, subjective memory complaints were associated with impaired higher-level functional capacity after adjustment for age and depressive symptoms (OR=3.36; 95% confidence interval [CI], 1.59-7.08). Among the men, subjective memory complaints were not significantly associated with impaired higher-level functional capacity after adjustment for age and depressive symptoms (OR=1.91; 95% CI, 0.88-4.12). CONCLUSIONS: Subjective memory complaints among women can indicate impaired higher-level functional capacity and may suggest higher one-year mortality rates.

Associations between Depressive State and Impaired Higher-Level Functional Capacity in the Elderly with Long-Term Care Requirements.

Depressive state has been reported to be significantly associated with higher-level functional capacity among community-dwelling elderly. However, few studies have investigated the associations among people with long-term care requirements. We aimed to investigate the associations between depressive state and higher-level functional capacity and obtain marginal odds ratios using propensity score analyses in people with long-term care requirements. We conducted a cross-sectional study based on participants aged ≥ 65 years (n = 545) who were community dwelling and used outpatient care services for long-term preventive care. We measured higher-level functional capacity, depressive state, and possible confounders. Then, we estimated the marginal odds ratios (i.e., the change in odds of impaired higher-level functional capacity if all versus no participants were exposed to depressive state) by logistic models using generalized linear models with the inverse probability of treatment weighting (IPTW) for propensity score and design-based standard errors. Depressive state was used as the exposure variable and higher-level functional capacity as the outcome variable. The all absolute standardized differences after the IPTW using the propensity scores were < 10% which indicated negligible differences in the mean or prevalence of the covariates between non-depressive state and depressive state. The marginal odds ratios were estimated by the logistic models with IPTW using the propensity scores. The marginal odds ratios were 2.17 (95%CI: 1.13-4.19) for men and 2.57 (95%CI: 1.26-5.26) for women. Prevention of depressive state may contribute to not only depressive state but also higher-level functional capacity.

Selection of rodent species appropriate for mtDNA transfer to generate transmitochondrial mito-mice expressing mitochondrial respiration defects.

Previous reports have shown that transmitochondrial mito-mice with nuclear DNA from Mus musculus and mtDNA from M. spretus do not express respiration defects, whereas those with mtDNA from Rattus norvegicus cannot be generated from ES cybrids with mtDNA from R. norvegicus due to inducing significant respiration defects and resultant losing multipotency. Here, we isolated transmitochondrial cybrids with mtDNA from various rodent species classified between M. spretus and R. norvegicus, and compared the O2 consumption rates. The results showed a strong negative correlation between phylogenetic distance and reduction of O2 consumption rates, which would be due to the coevolution of nuclear and mitochondrial genomes and the resultant incompatibility between the nuclear genome from M. musculus and the mitochondrial genome from the other rodent species. These observations suggested that M. caroli was an appropriate mtDNA donor to generate transmitochondrial mito-mice with nuclear DNA from M. musculus. Then, we generated ES cybrids with M. caroli mtDNA, and found that these ES cybrids expressed respiration defects without losing multipotency and can be used to generate transmitochondrial mito-mice expressing mitochondrial disorders.

Role of histamine and its receptor subtypes in stimulation of conjunctival goblet cell secretion.

PURPOSE: The purpose of this study was to determine the effect of histamine and its receptors on goblet cell secretion. METHODS: Cultured rat and human goblet cells were grown in RPMI 1640. Goblet cell secretion of high molecular weight glycoconjugate was measured by an enzyme-linked lectin assay. Cultured rat goblet cells were homogenized and either RNA was isolated for RT-PCR or proteins were isolated for Western blot analysis for presence of histamine receptors subtypes H1 through H4. The localization of these receptors was determined in rat and human goblet cells by immunofluorescence microscopy. RESULTS: Histamine stimulated goblet cell secretion in a concentration- and time-dependent manner. All four histamine receptors were present in cultured rat and human goblet cells. Use of agonists specific to individual histamine receptor subtypes indicated that the rank order of agonist stimulation was H1 = H3 > H4 > H2. Using antagonists specific to individual histamine receptor subtypes determined that H2 and H3, but not the H1 and H4, antagonists, inhibited histamine-stimulated conjunctival goblet cell secretion. CONCLUSIONS: Rat and human conjunctival goblet cells are a direct target of histamine, which induces secretion. All four histamine receptors are present in rat and human conjunctiva and are active in rat conjunctival goblet cells. These findings suggest that all four histamine receptor subtypes are important for conjunctival goblet cell secretion. Blockage of histamine receptor subtypes could prevent the excess mucus production associated with ocular allergy.