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Aim: The coronavirus disease 2019 (COVID-19) pandemic has led to lifestyle restrictions and might be associated with long-term changes in cognitive function. The aim of the present study was to elucidate the overall effect of the COVID-19 pandemic on the cognitive trajectory of a cohort of patients with cognitive impairment., Methods: We enrolled 160 patients who had been making regular visits to a medical center for dementia. Cognitive function was assessed based on changes in scores on the Mini-Mental State Examination before and during the COVID-19 pandemic throughout a 4-year period. The trajectory of cognitive decline was determined by carrying out a time series analysis using a state-space model., Results: Crude analysis showed that the Mini-Mental State Examination scores decreased from 20.9 ± 4.4 points (mean ± SD) at the time of the initial cognitive assessments to 17.5 ± 5.6 points at the time of the final assessments, and the decline rate was 1.15 ± 1.78 points per year (P < 0.0001). The time series analysis showed an accelerated cognitive trajectory after the COVID-19 outbreak, and the average decline in the Mini-Mental State Examination scores was 0.46 points (95% confidence interval 0.034-0.91) per year before the COVID-19 pandemic, and a steeper decline of 1.87 points (95% confidence interval 1.34-2.67) per year after the outbreak., Conclusions: The COVID-19 pandemic accelerated the rate of cognitive decline in patients with cognitive impairment fourfold in comparison with before the pandemic. Specific strategies designed for cognitively older people in the "new normal" will reconcile both requirements, reducing the risk of infection, and maintaining their physical and psychological well-being. Geriatr Gerontol Int 2023; 23: 200-204., (© 2023 Japan Geriatrics Society.)

The plasmid is a very well-known mobile genetic element that participates in the acquisition of virulence genes, such as staphylococcal enterotoxins (SEs), via horizontal transfer. SEs are emetic toxins and causative agents in staphylococcal food poisoning (SFP). We herein identified the types of plasmids harbored by seven SFP isolates and examined their production of plasmid-related SE/SEl to determine whether the new types of plasmid-related SE or SE-like (SEl) toxins (i.e. SElJ and SER) were involved in SFP. These isolates harbored pIB485-like plasmids, and all, except for one isolate, produced SElJ and SER. The amount of SER produced by each isolate accounted for the highest or second highest percentage of the total amount of SE/SEl produced. These new types of plasmid-related SE/SEls as well as classical SE may play a role in SFP. The seven isolates were classified into two SED-production types; a high SED-production type (>500 ng/ml) and no SED-production type. A nucleotide sequencing analysis revealed that three plasmids harbored by the SED-non-producing isolates had a single-base deletion in the sed gene with a resulting stop codon (from 233 amino acids of the intact SED to 154 amino acids of the mutant SED (mSED)). A real-time reverse transcription-PCR analysis showed that the mRNA of the msed gene was transcribed in the isolates. If the msed gene was translated as a protein, mSED may act as an emetic toxin instead of intact SED.

Drug resistance trends were investigated for 1,318 enterotoxigenic Escherichia coli (ETEC) isolated from overseas traveler's diarrheal cases in Tokyo during 1988-1999. A total of 1.6% (21 strains) were nalidixic-acid resistant and fluoroquinolones (NFLX, OFLX, CPFX, LVFX, TFLX, SPFX; FQ) low-sensitive (or low-level-resistant). None of the strains were high-level-resistant to FQ. The FQ low-sensitive strains were isolated in 1996 for the first time, and increased from 3.4% in 1996 to 15.8% in 1999. Countries visited by travelers with the FQ low-sensitive ETEC were India (16 cases), Nepal (3 cases), Cambodia (1 case), and Egypt (1 case). Drug resistance-patterns of the FQ low-sensitive strains, including other drugs (CP, TC, SM, KM, ABPC, ST, NA, and FOM) tested, varied among the 6 types. Among those, multidrug resistant strains accounted for 57.1% (12 strains). The enterotoxin producing types of strains were LT (4 strains), ST (10 strains), and both (7 strains). The serotypes of the strains were classified into 16 types. The quinolone resistance determining regions (QRDRs) of the gyrA genes of the FQ low-sensitive strains were sequenced. The mutations of a Ser to a Leu at position 83 (Ser-83-->Leu) was found in 19 strains, and Asp-87-->Tyr was found in 2 strains.

A total of 118 nalidixic-acid (NA)-resistant Salmonella strains consisting of 68 domestic strains and 50 imported strains isolated during 1988-1998 in Tokyo were examined regarding their annual incidence, serovars, drug-resistance patterns, and minimum inhibitory concentrations(MIC) to fluoroquinolones (NFLX, OFLX, ENX, and CPFX). NA-resistant strains accounted for 1.3% of all Salmonella (5,302 strains) isolated from domestic cases, and 2.5% of all Salmonella (1,981 strains) isolated from imported cases. The incidence of NA-resistant strains has increased since 1995, and it has been remarkable in imported cases. The results of the serotyping showed that the NA-resistant strains were classified into 25 serovars, excluding untypable strains. Among those, S. Enteritidis (21 strains), S. Blockley (13 strains), S. Litchifield (13 strains), S. Typhimurium (13 strains), S. Hadar (9 strains), and S. Virchow (8 strains) were predominant. Drug-resistance patterns of NA-resistant strains, including other drugs (CP, TC, SM, KM, ABPC, ST, FOM, and NFLX) tested varied among the 26 types. Among those, multidrug-resistant strains accounted for 61.9% (73 strains), and one strain among them was high-resistant to NFLX. MIC distribution of NA-resistant strains to fluoroquinolones showed that the ranges of all drugs were 4-128 times higher than NA-sensitive strains used for controls.

A total of 780 Salmonella serovar Hadar (S. Hadar) strains consisting of 601 domestic strains and 179 imported strains isolated in Tokyo, 1980-1998, were examined regarding their incidence and drug-resistance. Domestic strains accounted for 7.2% of all Salmonella (8,359 strains) isolated from domestic cases, and imported strains accounted for 4.4% of all Salmonella (4,083 strains) isolated from imported cases. A drug-resistance test using 9 drugs (CP, TC, SM, KM, ABPC, ST, NA, FOR, and NFLX) showed that 586 strains (97.6%) of the domestic strains and 175 strains (97.8%) of the imported strains were resistant to some of the drugs, excluding NFLX. Drugs with a high resistance rate were TC and SM for both groups. Drug-resistance patterns of the resistant strains varied among the 24 types. Among those, prevalent patterns recognized were TC.SM.KM (231 strains), TC.SM (205 strains), and TC.SM.KM.ABPC (65 strains) in the domestic strains, and TC.SM (135 strains) and TC (13 strains) in the imported strains.

A total of 341 Shigella sonnei strains consisting of 94 domestic strains and 247 imported strains isolated during 1990-1997 in Tokyo, were examined regarding their colicine-type, drug-resistance and ornithine-utilization. The colicine typing results showed that the domestic strains were classified into 7 types, and the imported strains were classified into 13 types. Among the colicine-types identified, 8-type, 0-type, 6-type and 12-type were predominant in the domestic strains, whereas 6-type, 0-type, 8-type, 9A-type and 12-type were predominant in the imported strains. The drug-resistance test using 9 drugs (CP, TC, SM, KM, ABPC, ST, NA, FOM and NFLX) showed that 89.4% of the domestic strains and 85.4% of the imported strains were resistant to some of the drugs except FOM and NFLX. Drugs with a high resistant rate were SM, TC and ST for both groups. Drug-resistance patterns of the resistant strains varied in 22 types. Among those, a triple drug-resistance type with TC.SM.ST was found in the most frequent pattern in both groups. The results of the ornithine-utilization test revealed that 28.7% of the domestic strains and 8.1% of the imported strains were negative. The ornithine-negative strains in the same source had a similar plasmid-profile, but generally there was no correlation between the different sources.

In a survey examining the causes of travellers' diarrhoea treated in Tokyo between July 1986 and December 1995, Aeromonas species were isolated from 1265 (5.5%) of 23,215 travellers returning from developing countries. Aeromonas species were the fourth most frequent enteropathogen isolated, following enterotoxigenic E. coli (8.5%), Salmonella spp. (7.6%) and Plesiomonas shigelloides (5.6%). Aeromonas species were found in 1191 (5.6%) of 21,257 patients with diarrhoea and in 74 (3.8%) of 1958 healthy individuals without diarrhoea. Mixed infection was observed in 512 (40.5%) cases. No significant difference in the prevalence of Aeromonas by year, season, age distributions, or sex was observed, but a slight difference was noted depending on the country where the travellers visited. Of the 1265 Aeromonas isolates, 893 strains (70.6%) were A. veronii biovar sobria, 330 (26.1%) were A. hydrophila, and 42 (3.3%) were A. caviae. The clinical symptoms of patients from whom Aeromonas species was isolated as the only potential enteric pathogen were almost similar, which were watery diarrhoea (about 60%), abdominal cramps (43%), fever (around 15%), and nausea or vomiting (13%). Although the severity of illness was milder than that of enterotoxigenic E. coli alone, these data suggest that Aeromonas species are important enteric pathogens in travellers' diarrhoea.

A total of 3,647 non-typhoidal Salmonella strains consisting of 2,655 domestic strains and 992 imported strains isolated in Tokyo from 1990 to 1994, were examined for their serovar-distribution and their drug-resistance. The serological typing results showed that the domestic strains were classified into 15 O-groups and 96 serovars, and the imported strains were classified into 13 O-groups and 73 serovars. Among the serovars identified, Salmonella serovar Enteritidis (S. Enteritidis), S. Thompson, S. Hadar, S. Litchfield, and S. Tennessee were predominant in the domestic strains, whereas S. Hadar, S. Enteritidis, S. Anatum, S. Derby, and S. Blockley were predominant in the imported strains. The drug-resistance test using 9 drugs (CP, TC, SM, KM, ABPC, ST, NA, FOM, and NFLX) showed that 30.5% of the domestic strains and 40.5% of the imported strains were resistant to any of the drugs examined. The serovars of a high resistant rate during this period were S. Hadar (96.2%), S. Blockley (88.7%), S. Enteritidis (63.4%), S. Virchow (54.3%), and S. Typhimurium (51.3%) in the domestic strains and S. Krefeld (100%), S. Hadar (98.9%), S. Blockley (98.2%), S. Emek (83.3%), S. Kentucky (76.5%), S. Panama (69.2%), S. Derby (63.8%), S. Typhimurium (57.1%), S. Rissen (55.6%), and S. Agona (53.7%) in the imported strains. Drug-resistance patterns of the resistant isolates varied to 62 types. Prevalent patterns recognized were SM, TC.SM, TC.SM.KM, TC, TC.SM.KM.ABPC and CP.TC.SM.KM in the domestic strains and TC.SM, TC, CP.TC.SM.ST, TC.SM.KM, and CP.TC.SM.KM in the imported strains.

A total of 446 Shigella strains consisting of 336 imported and 110 domestic strains isolated in Tokyo from 1990 to 1994 were examined for their species and serovar-distribution, and their drug-resistance. In both imported and domestic strains, S. sonnei was found to be the most prevalent species, followed by S. flexneri. In imported strains, however, the isolation frequency of S. flexneri, S. boydii and S. dysenteriae were higher than that of domestic strains, and the serovar of each species was distributed in a wider range than that of the domestic strains. Provisional new serovar Shigella strains were isolated from 8 imported cases and 2 domestic cases. The drug-resistance-test using 9 drugs (CP, TC, SM, KM, ABPC, ST, NA, FOM, and NFLX) showed that 82.7% of the imported strains and 89.1% of the domestic strains were resistant to any drugs examined. Drugs of a high resistant rate were SM, TC, ST for the both groups. Drug-resistance-patterns of the resistant isolates varied to 21 types. Among those, a triple drug-resistance-type with TC SM ST was found the most frequently in both groups. None of the strains were resistant to FOM or NFLX.

Two Shigella strains (85-634 and 94-30) isolated from two sporadic travellers with diarrhea who returning to Tokyo from abroad, did not react to any antisera to Shigella prepared commercially. These strains had the typical biochemical characteristics of S. boydii and were biochemically identical, and were positive in the Serény test and other tests for invasiveness; these indicate that they can cause shigellosis in humans. The results of serological analyses using the antisera to 6 kinds of provisional Shigella serovars, showed that both strains had provisional S. boydii serovar E16553. Although the serovar has been reported by Gross et al in the United Kingdom, this may be the first report in Japan.

In 1992, the number of cases of shigellosis in Tokyo increased remarkably, and a total of 10 separate outbreaks were confirmed. Except for 1 series where the causative strains was Shigella flexneri 3a, the other 9 outbreaks were caused by Shigella sonnei. Of note, 7 outbreaks were familial with less than 5 patients. The remaining 3 outbreaks occurred in a restaurant, a school and the dormitory of an orphanage, in which the organism was detected in 6 to 14 patients. In 4 of the familial outbreaks occurring in distant areas during August, ark shell was presumed to be the vehicle by epidemiological investigations and laboratory examinations. Analysis of isolates such as the antibiotic resistance pattern, plasmid profile, or colicine type in Shigella sonnei was useful in clarifying the commonality of each case and identifying the vehicle or transmission.

Seven thousand three hundred seventy-six sudden or violent manner of deaths were inspected or autopsied at Tokyo Metropolitan Medical Examiner's Office in 1989. Out of these victims, 693 (9.4%) victims were regarded as heavy drinkers on the basis of the drinking habits and the autopsy reports and 196 (2.7%) victims without past problem drinking were thought to be drunk at death from the family statements or the blood alcohol analysis. The total 889 (12.1%) alcohol-related cases (autopsy was performed on the 489 cases) were studied from epidemiological and etiological viewpoints. The average age of the alcohol-related victims (male: 811, female: 78) was 52 +/- 11 years. In middle-aged (45-54 years) men, 34% of the all sudden or violent deaths were alcohol-related. About half of the alcohol-related victims were living alone and jobless and they often died at home, particularly in the bed. In the alcohol-related victims, the blood alcohol concentration (BAC) analysis revealed that the average BAC of female was significantly higher than that of male. (2.12 +/- 1.73 mg/ml vs. 1.33 +/- 1.75, P < 0.01). This difference may be associated with sex difference in ethanol metabolism, body composition and drinking habits. Among the major causes of the alcohol-related deaths, alcoholic liver diseases accounted for 226 (25%), gastro-intestinal bleedings for 115 (13%), cardiovascular diseases for 105 (12%) and violent deaths (e.g., acute alcohol intoxication, falls, traffic accidents, suicide) for 329 (37%). By histopathological examination of the liver, about 30% of the alcoholic liver disease cases showed mainly fatty metamorphosis and 48% showed liver cirrhosis. Only 12% of the cirrhotics had either jaundice or ascites, suggesting hepatic failure. Alcoholic cardiomyopathy was suspected in only 11 cases. In conclusion, many people, particularly middle-aged men, lose their lives due to heavy drinking and there are many pathologically unexplainable sudden deaths of alcoholics.

The prevalence, rate of correct clinical diagnosis and mortality of cancer were analyzed in 4,894 consecutive autopsies at the Tokyo Metropolitan Geriatric Hospital from 1972 to 1990. average age and standard deviation of patients was 78.1 +/- 9.1 years. Cancer was found in 45.5% of patients of 60 years and over, and in 49.1% in men and 41.9% in women (p < 0.001). Cancer prevalence decreased with advance in age; 50.0% in the sixties, 47.9% in the seventies, 43.2% in the eighties and 39.3% in the nineties and over. Multiple cancer was found in approximately 12% of patients of 70 years and over. The top three cancer incidences were gastric cancer, 15.0%, lung cancer, 10.7% and colon cancer, 5.9% in both genders. In men, prostate cancer was next common, followed in orderly hepatic cancer, esophageal cancer, gall bladder-bile duct cancer, pancreas cancer, renal cancer and urinary bladder cancer. In women, the following order of frequency was gall bladder-bile duct cancer, uterus cancer, pancreas cancer, hepatic cancer, breast cancer, thyroid cancer, esophageal cancer, renal cancer and urinary bladder cancer. The prevalence of gastric cancer, lung cancer, hepatic cancer and esophageal cancer was significantly higher in men, while that of gall bladder-bile duct cancer was higher in women. The age-related tendencies varied among cancers of different organs. Gastric cancer increased up to the sixties in men and up to the seventies in women and leveled off after those ages. Lung cancer revealed peak prevalence in the sixties and seventies and decreased after the age of eighty.(ABSTRACT TRUNCATED AT 250 WORDS)

A total of 6,816 strains of nontyphoidal Salmonella isolated from oversea travellers (imported cases) and domestic healthy individuals and sporadic cases (domestic cases) in Tokyo from 1980 to 1989 were studied for their serovar distribution and antimicrobial sensitivity. The serological typing results showed that the Salmonella strains were classified into 22 O groups and 156 serovars. Among serovars identified, S. ser. Anatum, S. ser. Derby, S. ser. Blockley, S. ser. Agona and S. ser. Typhimurium were predominant in imported cases, while S. ser. Litchfield, S. ser. Typhimurium, S. ser. Hadar, S. ser. Infantis and S. ser. Thompson were predominant in domestic cases. It was also noticed that isolation rates of S. ser. Hadar and S. ser. Blockley have tended to increase noticeably in recent years in both cases. From antimicrobial sensitivity testing, 739 (28.1%) of 2,628 strains isolated from imported cases and 1,047 (25.0%) of 4,188 strains isolated from domestic cases were found to be resistant to any one of the drugs tested (CP, TC, SM, KM, ABPC, ST, NA, FOM and NFLX). From 1980 to 1983 the resistance rate was less than 20% for both cases and then the rate was increased year by year, and it became greater than 40% in 1989. Serovars of a high resistant rate during this period were S. ser. Hadar (96.3%), S. ser. Blockley (92.0%), S. ser. Typhimurium (75.7%), S. ser. Kentuckey (64.1%), S. ser. Krefeld (59.3%), and S. ser. Panama (58.3%) for the imported cases and S. ser. Hadar (97.5%), S. ser. Blockley (57.4%), S. ser. Litchfield (44.6%), S. ser. Enteritidis (44.4%), S. ser. Muenchen (42.2%) and S. ser. Typhimurium (40.9%) for the domestic cases. Drug resistance patterns of the resistant isolates varied up to as much as 50 patterns. Prevalent patterns recognized were TC.SM, CP.TC.SM.KM, TC, CP.TC.SM.KM.ABPC and SM for imported cases and TC.SM, TC, TC.SM.KM, SM, and CP.TC for the domestic cases. 21(12.4%) of 170 drug resistant strains were isolated from imported cases from 1988 to 1989 were found to have conjugative transmissible R plasmids.

A total of 1,189 Shigella strains consisting 804 imported and 385 domestic strains were examined for their species and serovar distribution, and their drug-resistance. In both imported and domestic strains, S. sonnei was found to be the most prevalent species, followed by S. flexneri, S. boydii and S. dysenteriae in order. In imported strains, however, the isolation frequency of S. flexneri, S. boydii and S. dysenteriae were higher than that of domestic strains, and the serovar of each species was distributed in a wider range than that of the domestic strains. The drug resistance test using chloramphenicol (CP), tetracycline (TC), streptomycin (SM), kanamycin (KM), ampicillin (ABPC), sulfamethoxazole-trimethoprim (ST), nalidixic acid (NA), fosfomycin (FOM) and norfloxacin (NFLX) showed that 80.1% of the imported strains and 82.9% of the domestic strains were resistant to any of drugs examined, although frequency of resistance varied by their species. The frequency of resistance to each drugs were SM (74.0%), TC (68.5%), CP (38.8%), ABPC (35.3%), ST (34.1%), NA (1.5%) and KM (1.0%) in imported strains, and TC (79.2%), SM (55.3%), ABPC (40.3%), CP (38.4%), ST (32.4%), NA (30.5%) and KM (4.2%) in domestic strains. No strain resistant to FOM or NFLX was found in both groups. The resistance patterns varied to 32 types. Among those, a multiple drug-resistance type with CP.TC.SM.ABPC was found most frequently in both groups. Frequency of strains carrying transferable R plasmid was tested for 50 strains isolated in 1989 and three (6%) of them had the plasmid.