Impact of the COVID-19 Pandemic on Older People's Loneliness: Findings from a Longitudinal Study between 2019 and 2021 among Older Home-Dwellers in Finland.

OBJECTIVES: To investigate the change in feelings of loneliness among Finnish community-dwelling older people from before the COVID-19 pandemic in 2019 to during the pandemic in 2021. Moreover, we explore the changes in other dimensions of psychological well-being (PWB) during the study period. DESIGN: Questionnaires were mailed in the 2019 Helsinki Aging Study, a repeated cohort study. A follow-up interview was carried on over the telephone during the year 2021. SETTING AND PARTICIPANTS: A random sample of 2,917 home-dwelling older people aged 75-104 years residing in Helsinki, Finland were mailed the questionnaire. Altogether 898 participated in the follow-up. MEASUREMENTS: Loneliness was measured using a single item question "Do you suffer from loneliness?". Other items of psychological well-being were measured: "Are you satisfied with your life?" (yes/no), "Do you feel useful?" (yes/no), "Do you have a zest for life?" (yes/no),"Do you have plans for the future?" (yes/no), and "Do you feel depressed?"("rarely or never"/ "sometimes"/ "often or always"). RESULTS: Altogether 898 people participated both in 2019 and 2021. The subjects' mean age was 83 years and 66% were women. Between 2019 and 2021, the prevalence of experienced loneliness increased among older home-dwellers from 26% to 30%. During two years of the pandemic feelings of loneliness (RR 1.79, 95% CI: 1.30 to 2.46) and depression (RR 1.37, 95% CI: 1.12 to 1.67) increased even adjusted with various confounders. CONCLUSION: Considering the impact loneliness has on health and well-being, the finding of increased feelings of loneliness among older people is alarming. Actions to combat loneliness need to be taken.

Prevalence of Musculoskeletal Pain and Analgesic Treatment Among Community-Dwelling Older Adults: Changes from 1999 to 2019.

BACKGROUND: Pain is undertreated in older populations. At the same time, increased use of opioids is of concern in the Western world. AIMS: We sought to analyze temporal trends in musculoskeletal pain and prescribed analgesic treatment among community-dwelling people aged 75-95 years using cross-sectional cohort data spanning 20 years. METHODS: The Helsinki Aging Study recruited random samples of people aged 75, 80, 85, 90, and 95 years in 1999, 2009, and 2019. In total, 5707 community-dwelling persons participated in the study. The participants reported their medical diagnoses, regular prescription medications, and the presence of back pain or joint pain within the last 2 weeks (never, sometimes, or daily). We compared analgesic use among participants reporting and not reporting musculoskeletal pain in 1999, 2009, and 2019. RESULTS: Of the participants, 57-61% reported intermittent or daily musculoskeletal pain. The percentage receiving a prescribed daily analgesic increased from 9% in 1999 to 16% in 2019. The use of non-steroidal anti-inflammatory drugs (NSAIDs) decreased from 1999 to 2019, while the use of paracetamol increased from 2 to 11%. Opioids were taken by 2% in 1999 and 3% in 2019. Of those reporting daily musculoskeletal pain, 20%, 35%, and 32% received regular pain medication in 1999, 2009, and 2019, respectively. CONCLUSIONS: Pain remains undertreated in the community-dwelling older population, although the use of regular prescribed analgesics increased between 1999 and 2019. The use of NSAIDs has decreased, while the use of paracetamol has increased. Daily opioid use has remained modest.

Symptom burden in community-dwelling older people: temporal trends in the Helsinki Aging Study.

BACKGROUND: Changes in older people's symptoms across recent decades have not been investigated. AIMS: We analyzed temporal trends in symptom burden by comparing data from independent, cross-sectional cohorts retrieved in 1989, 1999, 2009, and 2019. Furthermore, we compared the association between symptom burden and psychological wellbeing (PWB) in older men and women. METHODS: The Helsinki Aging Study recruited a random sample of people aged 75, 80, and 85 in 1989, and random samples aged 75, 80, 85, 90, and 95 in 1999, 2009, and 2019 (four study waves). Altogether, 6263 community-dwelling people answered the questions concerning symptoms in the questionnaire surveys. The symptoms inquired in all study waves were dizziness, back pain, joint pain, chest pain, shortness of breath, and loss of appetite. Symptom burden was calculated according to the number of symptoms and their frequency (score range: 0-6). PWB and the Charlson comorbidity index were calculated. RESULTS: Symptom burden decreased in both men and women aged 75 and 80 from 1989 to 2019. Changes in cohorts aged 85 + were nonsignificant. There was a significant difference in symptom burden between men and women in all ages with men having fewer symptoms. PWB decreased with increasing symptom burden. Men had greater PWB than women up to severe levels of symptom burden. CONCLUSIONS: Symptom burden decreased from 1989 to 2019 in cohorts aged 75-80, whereas changes remained nonsignificant in cohorts aged 85 +. To our knowledge, this is the first study to examine temporal trends in symptom burden.

The sarcopenia and physical frailty in older people: multi-component treatment strategies (SPRINTT) project: description and feasibility of a nutrition intervention in community-dwelling older Europeans.

BACKGROUND: The "Sarcopenia and Physical Frailty in Older People: Multicomponent Treatment Strategies" (SPRINTT) project sponsored a multi-center randomized controlled trial (RCT) with the objective to determine the effect of physical activity and nutrition intervention for prevention of mobility disability in community-dwelling frail older Europeans. We describe here the design and feasibility of the SPRINTT nutrition intervention, including techniques used by nutrition interventionists to identify those at risk of malnutrition and to carry out the nutrition intervention. METHODS: SPRINTT RCT recruited older adults (≥ 70 years) from 11 European countries. Eligible participants (n = 1517) had functional limitations measured with Short Physical Performance Battery (SPPB score 3-9) and low muscle mass as determined by DXA scans, but were able to walk 400 m without assistance within 15 min. Participants were followed up for up to 3 years. The nutrition intervention was carried out mainly by individual nutrition counseling. Nutrition goals included achieving a daily protein intake of 1.0-1.2 g/kg body weight, energy intake of 25-30 kcal/kg of body weight/day, and serum vitamin D concentration ≥ 75 mmol/L. Survey on the method strategies and feasibility of the nutrition intervention was sent to all nutrition interventionists of the 16 SPRINTT study sites. RESULTS: Nutrition interventionists from all study sites responded to the survey. All responders found that the SPRINTT nutrition intervention was feasible for the target population, and it was well received by the majority. The identification of participants at nutritional risk was accomplished by combining information from interviews, questionnaires, clinical and laboratory data. Although the nutrition intervention was mainly carried out using individual nutritional counselling, other assisting methods were used as appropriate. CONCLUSION: The SPRINTT nutrition intervention was feasible and able to adapt flexibly to varying needs of this heterogeneous population. The procedures adopted to identify older adults at risk of malnutrition and to design the appropriate intervention may serve as a model to deliver nutrition intervention for community-dwelling older people with mobility limitations.

Symptom Burden Is Associated with Psychological Wellbeing and Mortality in Older Adults.

IMPORTANCE: Over half of outpatient visits are due to physical symptoms; yet, the significance of symptoms in relation to older people's wellbeing and prognosis has gained very little research attention. OBJECTIVES: This study aims to analyze the prognostic value of symptom burden, derived from symptom count and frequency, in an older cohort aged 75 to 95. We also explore the association between symptom burden and psychological wellbeing. DESIGN: Randomly assigned cohorts of community-dwelling people aged 75-95 filled in the postal questionnaire of the Helsinki Aging Study in 2009. SETTING: Community-based, postal questionnaires (survey response rate 74%). PARTICIPANTS: 1583 community-dwelling people aged 75-95 in the urban Helsinki area. Main outcomes and measures: The inquired symptoms were dizziness, back pain, joint pain, chest pain or discomfort, shortness of breath, leg pain when walking, loss of appetite, and urinary incontinence. Symptom burden was calculated according to the number of symptoms and their frequency (score range: 0-8). The participants were subdivided into four groups according to their symptom burden. Mortality data was extracted from the Finnish Population Register in 2014. Psychological wellbeing (PWB) was measured using the validated PWB score. RESULTS: Of 1583 participants, 18% reported no symptoms over the past 2 weeks (Group 0), 31% scored 0.5-1 in the symptom burden score (Group 1), 23% scored 1.5-2 (Group 2), and 28% scored 2.5-8 (Group 3). There was a linear relationship between symptom burden and comorbidities, functional status, falls, and PWB. The groups showed a significant difference in 5-year mortality, even adjusted for age, sex, and comorbidities: Group 1 1.18, 95% CI 0.84-1.66; Group 2 1.63, 95% CI 1.15-2.31, and Group 3 2.08, 95% CI 1.49-2.91 compared to Group 0 (p for linearity <0.001). Conclusion and relevance: Symptom burden is associated with higher mortality and lower PWB independent of comorbidities in community-dwelling people aged 75-95. We conclude that somatic symptoms need to be assessed when examining the general health status of an aging patient. Self-reported symptoms seem to convey information about health that cannot be derived from medical diagnoses only.

Relationship between Anticholinergic Burden and Health-Related Quality of Life among Residents in Long-Term Care.

OBJECTIVES: Anticholinergic burden defined by the Anticholinergic Risk Scale (ARS) has been associated with cognitive and functional decline. Associations with health-related quality of life (HRQoL) have been scarcely studied. The aim of this study was to examine the association between anticholinergic burden and HRQoL among older people living in long-term care. Further, we investigated whether there is an interaction between ARS score and HRQoL in certain underlying conditions. DESIGN AND PARTICIPANTS: Cross-sectional study in 2017. Participants were older people residing in long-term care facilities (N=2474) in Helsinki. MEASUREMENTS: Data on anticholinergic burden was assessed by ARS score, nutritional status by Mini Nutritional Assessment, and HRQoL by the 15D instrument. RESULTS: Of the participants, 54% regularly used ARS-defined drugs, and 22% had ARS scores ≥2. Higher ARS scores were associated with better cognition, functioning, nutritional status and higher HRQoL. When viewing participants separately according to a diagnosis of dementia, nutritional status or level of dependency, HRQoL was lower among those having dementia, worse nutritional status, or being dependent on another person's help (adjusted for age, sex, comorbidities). Significant differences within the groups according to ARS score were no longer observed. However, interactions between ARS score and dementia and dependency emerged. CONCLUSION: In primary analysis there was an association between ARS score and HRQoL. However, this relationship disappeared after stratification by dementia, nutritional status and dependency. The reasons behind the interaction concerning dementia or dependency remain unclear and warrant further studies.

Serum antibody response to Chlamydia trachomatis TroA and HtrA in women with tubal factor infertility.

Persistent genital chlamydial infection may lead to tubal factor infertility (TFI). Chlamydia trachomatis TroA and HtrA are proteins expressed during persistent chlamydial infection in vitro. We studied serum IgG antibody response against these proteins by EIA in women with TFI and in subfertile women without tubal pathology. Altogether, 22 of 258 subfertile women (8.5%) had TFI which was unilateral in 17 cases and bilateral in 5 cases. Overall, 55 (21.3%) of the 258 women had TroA and 39 (15.1%) had HtrA antibodies. Seropositivity to TroA and HtrA was more common among women with TFI than women with other causes for subfertility (45.5 vs. 19.1%, p = 0.004 for TroA; 36.4 vs. 13.1%, p = 0.004 for HtrA). Mean absorbance values and the prevalence of TroA and HtrA antibodies increased with increasing severity of TFI. On the basis of our results, TroA and HtrA serology has the potential to be further developed to a specific biomarker for C. trachomatis-related TFI.

Contribution of IL-12A and IL-12B polymorphisms to Chlamydia trachomatis-specific cell-mediated immune responses.

Inherited variance in the IL-12B gene is associated with susceptibility to Chlamydia trachomatis-induced tubal factor infertility and disease severity. In this study, our aim was to discover how polymorphisms in IL-12-coding genes influence C. trachomatis-induced immune responses and IL-12 production. The study population consisted of 240 women. IL-12A and IL-12B single nucleotide polymorphisms (SNPs) were determined from isolated DNA using the Sequenom system with matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. We studied lymphocyte proliferative (LP) responses to C. trachomatis strains E and F elementary bodies (EBs) and recombinant chlamydial heat-shock protein 60 (CHSP60) antigen. IL-12p40 and IL-12p70 levels were measured using the BD Flex Set method. We found a statistically significant association between the C. trachomatis EB antigen-specific LP response and the rs2853694 SNP (P = 0.02). Our study demonstrates that the IL-12 cytokine family is involved in C. trachomatis-specific immune responses. Moreover, C. trachomatis-induced IL-12 production and the IL-12B rs2853694 SNP partially explain individual variation in the C. trachomatis LP response.

Effect of IL12A and IL12B polymorphisms on the risk of Chlamydia trachomatis-induced tubal factor infertility and disease severity.

BACKGROUND: Interleukin-12 (IL-12) and related cytokines induce activation and differentiation of T cells. Our aim was to investigate the associations between genetic differences in IL-12-family cytokines and the pathogenesis of chlamydial disease. METHODS: The final study population consisted of 100 women with Chlamydia trachomatis-induced tubal factor infertility (TFI) and 125 pregnant women as controls. Three single nucleotide polymorphisms (SNPs) of IL12A and seven SNPs of IL12B genes were determined from isolated DNA using the Sequenom system with matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. RESULTS: We found that the IL12B SNP rs3212227 was associated with both susceptibility and severity of TFI. The minor allele C was rare and only one CC homozygote was found among the controls. AC heterozygotes were more common among TFI cases than among controls (P = 0.009) and were associated with increased risk of TFI [odds ratios (OR) = 2.44, 95% confidence intervals (CI) = 1.23-4.87]. Carrying the minor allele C was also associated with disease severity (P for trend = 0.008) and moderate (OR = 2.51, 95% CI = 1.06-5.95) and severe tubal damage (OR = 2.73, 95% CI = 1.15-6.52). CONCLUSIONS: The results suggest that variation in the IL12B gene partly explains inter-individual differences in disease susceptibility and severity.

Cytokine gene polymorphism and Chlamydia trachomatis-specific immune responses.

Chlamydia trachomatis-induced fallopian tube damage leading to tubal factor infertility (TFI) is linked with TNF, IL-10, and probably IFNG gene polymorphisms. The aim of this study was to clarify the contribution of these cytokine gene polymorphisms to interindividual variation in C trachomatis-specific immune responses and the cross-regulation of secreted cytokines and single nucleotide polymorphisms (SNPs). Cytokine polymorphisms (IL-10 -1082A/G, -819T/C, and -592A/C, IFNG +874T/A, and TNF -308G/A) were genotyped by polymerase chain reaction in 139 women. C trachomatis-specific immune responses were measured using lymphocyte proliferation (LP) induced by C trachomatis E and F strains and chlamydial heat shock protein 60 antigens. Cytokine secretion was measured in culture supernatants of infected and uninfected mononuclear leukocytes. IL-10 -1082/-819/-592 and IFNG +874 SNPs were associated with the intensity of LP responses to C trachomatis antigens. These cytokines also interact with each other and a cumulative effect of IL-10 -1082 and IFNG +874 genotypes was seen in LP responses to C trachomatis antigens. Our data suggest that interleukin-10 and interferon-γ regulate C trachomatis-specific immune responses in humans and that genetic variation in the expression of their coding genes explains interindividual variation in host immune responses to C trachomatis infection.

Analyses of polymorphisms in the inflammasome-associated NLRP3 and miRNA-146A genes in the susceptibility to and tubal pathology of Chlamydia trachomatis infection.

Susceptibility to Chlamydia trachomatis infections is 40% host based. microRNA-146a is a negative regulator of Tolllike receptor (TLR) signaling and possesses functional polymorphisms which decrease the production of premiR-146a and mature miR-146a. Single nucleotide polymorphisms (SNPs) in NLRP3 are associated with decreased NLRP3 expression and hypoproduction of interleukin (IL)-1beta. We investigated whether the SNPs miR-146a G>C (rs2910164), NLRP3 C>T (rs4925663) and G>A (rs12065526) are associated with the susceptibility to and severity of C. trachomatis infection. The genotypes of three SNPs were tested in two cohorts: cohort 1 consists of Dutch women (n = 318) attending a sexually transmitted disease (STD) clinic and cohort 2 (n = 277) consists of subfertile (n = 184) and healthy Finnish women (n=93). While in cohort 1 the analyzed SNPs were not associated with the susceptibility to C. trachomatis infections (C. trachomatis-positive vs. C. trachomatis-negative), we showed in C. trachomatis-positive women that the NLRP3 mutant AG and AA genotypes were a risk factor for the development of symptoms (P = 0.047, OR = 2.9) and more specifically for having lower abdominal pain (genotype AA: P = 0.022, OR = 31.3). In the Finnish tubal pathology group versus the control group no statistical significant differences in the incidences of the SNPs studied were found, nor for the degree of tubal pathology. In conclusion, the mutant NLRP3 A allele is a risk factor for the development of symptoms, specifically lower abdominal pain, after a C. trachomatis infection in women attending an STD clinic.

Cytokine polymorphisms and severity of tubal damage in women with Chlamydia-associated infertility.

Chronic inflammation induced by Chlamydia trachomatis can lead to tubal factor infertility (TFI). To investigate the genetic basis of chlamydial TFI and various manifestations of tubal damage, we studied functional polymorphisms in selected cytokine genes (IL-10 -1082 A/G, -819 T/C, and -592 A/C; IFN-gamma +874 T/A; TNF-alpha -308 G/A; TGF-beta1 codons 10 T/C and 25 G/C; and IL-6 -174 G/C) in 114 women with laparoscopically verified TFI (hereafter known as "cases") and in 176 controls. Evidence of past infection with C. trachomatis was demonstrated in 96 cases by use of a combined test for humoral and cell-mediated immune responses to chlamydial elementary bodies (EBs) and chlamydial heat-shock protein 60 antigens. We found that the IL-10 -1082 AA genotype and the TNF-alpha -308 A allele increased the risk of severe tubal damage in women with infertility associated with C. trachomatis (odds ratio [OR], 7.3 [95% confidence interval {CI}, 1.3-42] and 4.0 [95% CI, 1.0-16], respectively), suggesting that differences in these genes contribute to the wide spectrum of disease manifestations.

IL-10 polymorphism and cell-mediated immune response to Chlamydia trachomatis.

Chlamydia trachomatis infection induces an inflammatory response that is crucial in resolving acute infection but may also play a key role in the pathogenesis of C trachomatis associated infertility. The immune response is linked to cytokine secretion pattern which is influenced by the host genetic background. To study a relationship between interleukin-10 (IL-10) promoter -1082 polymorphism and cell-mediated immune response during C trachomatis infection in vitro, lymphocyte proliferation and cytokine (IL-10, IFN-gamma, TNF-alpha, IL-2, IL-4 and IL-5) secretion were analysed in subjects with different IL-10 genotypes. Enhanced IL-10 secretion and reduced antigen-specific lymphocyte proliferative and IFN-gamma responses were found in subjects with IL-10 -1082 GG genotype when compared to those with -1082 AA genotype. CD14+ monocytes were main source of IL-10 indicating that these cells are important regulators of the antigen-specific cell-mediated responses during active C trachomatis infection. We conclude that impaired cell-mediated response to C trachomatis is associated with IL-10 genotype in subjects with high IL-10 producing capacity. A comparison of immune markers between subjects with a history of noncomplicated and complicated infection is needed to further understand the confounding factors associated with the development of C trachomatis associated sequelae.

The pH gradient over the stratum corneum differs in X-linked recessive and autosomal dominant ichthyosis: a clue to the molecular origin of the "acid skin mantle"?

In a search for pathogenetic mechanisms underlying retention hyperkeratosis, we examined the pH gradient over the stratum corneum in 13 male patients suffering from either x-linked recessive (XRI) or autosomal dominant ichthyosis vulgaris. For recording pH values, a flat glass electrode was repeatedly applied to the skin during tape stripping of mildly involved forearm skin. Before stripping, surface pH was higher in ichthyosis vulgaris (5.3 +/- 0.7; n = 7) than in XRI (4.6 +/- 0.4; n = 6; p < 0.05) and healthy control men (4.5 +/- 0.2; n = 7; p < 0.01). Removal of stratum corneum, which required 100-240 strippings in ichthyotic skin and 80-120 strippings in healthy control skin, disclosed markedly different pH variations in the two types of ichthyosis. The major abnormality in ichthyosis vulgaris skin was that a neutral pH was attained already halfway through the horny layer, possibly reflecting a congenital lack of acidic breakdown products from keratohyaline. By contrast, stripping of XRI skin revealed a shallow pH gradient that plateaued at 6.2-6.6, instead of about 7 as in normal and ichthyosis vulgaris skin. A likely explanation is the XRI-associated accumulation of cholesterol sulfate in lower stratum corneum. Our results suggest that the "acid mantle" of normal skin, which penetrates deep into the stratum corneum, is the combined result of cornification-associated organic acids and back-diffusion of acid material from the surface. Because corneocyte desquamation involves many pH-dependent enzymes, abnormalities in the transcorneal pH gradient might play a role in the pathogenesis of ichthyosis.

In vivo studies concerning a pH gradient in human stratum corneum and upper epidermis.

Human skin has an acid mantle of pH 4-6, contrasting with the almost neutral pH of the interior body and implying the existence of a pH gradient over the horny layer that might influence a variety of epidermal processes. In an attempt to characterize the pH gradient, we applied a glass electrode to the volar surface of the forearm before and after consecutive strippings with sello-tape. Before stripping, the surface pH (mean +/- SD) was 4.5 +/- 0.2 in men (n = 7) and 5.3 +/- 0.5 in women (n = 7), the values gradually increasing to pH 6.9 +/- 0.4 in men and 6.8 +/- 0.5 in women after about 100-120 tape strippings, which completely removed the stratum corneum. When plotted against the number of strippings, the pH values usually conformed to a sigmoid curve with inflection (50% change) after about 60 strippings, at a level corresponding histologically to the lower third of stratum corneum. Similar gradients were found also in skin of the abdomen and calf. Stripping with cyanoacrylate resin produced a similar gradient, even though this form of stripping was 10 times more effective. The healing process after tape stripping was studied by determining pH and transepidermal water loss in 5 persons over a period of 14 days. The importance of the re-established pH gradient is discussed in relation to the many pH-dependent enzymes operating in stratum corneum.

Cryptic plasmid of Neisseria gonorrhoeae: complete nucleotide sequence and genetic organization.

The naturally occurring cryptic plasmid pJD1 of Neisseria gonorrhoeae is 4,207 base pairs long and is found in about 96% of gonococcal strains. The total probable coding capacity of pJD1 was determined from the complete nucleotide sequence by using computational probes to identify open reading frames with similar codon usage and by screening for the presence of ribosomal binding sites before the start codons. Candidates for promoters and terminators were also found in the sequence. Based on these findings, we propose a model for the genetic organization of the plasmid. The model predicts two transcriptional units, each composed of five compactly spaced genes. A promoter of one of the transcripts was shown to function in Escherichia coli, and the products of three of the five genes in this operon were identified in minicell expression experiments. Of these, the cppA gene encoded a 9-kilodalton protein, and the cppB and cppC genes both coded for 24-kilodalton proteins. No expression of the other transcriptional unit was detected, but two genes in this operon were expressed in minicells when transcribed from an E. coli promoter. The experimental data were consistent with the model.