Syndrome of gingival hypertrophy, hirsutism, mental retardation and brachymetacarpia in two sisters: specific entity or variant of a described condition?

Two sisters born to consanguineous Lebanese parents had mental retardation and epilepsy, brachymetacarpalia, hirsutism, bulbous soft nose, thick floppy ears with abnormal configuration and gingival hypertrophy. One girl presented additionally with tetralogy of Fallot and the other with congenital hypothyroidism and bilateral ureteral stenosis. These manifestations resemble the syndrome of hypertrichosis-gingival fibromatosis-mental retardation and seizures of Anavi et al. [1989: Dev Med Child Neurol 31:538-542] but our two girls additionally have brachymetacarpia. The inheritance seems to be autosomal recessive. These two sisters may represent a hitherto undescribed syndrome. We discuss the findings in our patients in relation to the literature.     

Implementation failures in the use of two New Zealand laws to control the tobacco industry: 1989–2005

Background

We reviewed the implementation of New Zealand laws in relation to the activities of the tobacco industry and their allies. Material for two brief case studies was obtained from correspondence with official agencies, official information requests, internet searches (tobacco industry documents and official government sites), and interviews with 12 key informants.

Results

The first case study identified four occasions over a period of 14 years where New Zealand Government agencies appeared to fail to enforce consumer protection law, although apparent breaches by the tobacco industry and their allies had occurred in relation to statements on the relative safety of secondhand smoke. The second case study examined responses to a legal requirement for the tobacco industry to provide information on tobacco additives. There was failure to enforce the law, and a failure of the political process for at least 13 years to clarify and strengthen the law. Relevant factors in both these cases of 'policy slippage' appear to have been financial and opportunity costs of taking legal action, political difficulties and the fragmented nature of government structures.

Conclusion

Considered together, these case studies suggest the need for governments to: (i) make better use of national consumer laws (with proper monitoring and enforcement) in relation to tobacco; and (ii) to strengthen international law and resources around tobacco-related consumer protection. A number of options for achieving these aims are available to governments.

     

The epidemiology,clinical characteristics,and macrolide susceptibility of Mycoplasma pneumoniae pneumonia in children in Southern Taiwan, 2019–2020

BackgroundSince the global use of the pneumococcal conjugate vaccine, Mycoplasma pneumoniae (MP) has become the most common bacterial cause of lower respiratory tract infections among children. Monitoring the changing epidemiology and antimicrobial resistance rates of this organism is important for MP clinical management.MethodsThis study characterizes key features of MP during the 2019–2020 epidemic in children in Taiwan. The cohort included all hospitalized children under 18 years of age with polymerase chain reaction (PCR)-confirmed community-acquired mycoplasma pneumonia (CAMP) in southern Taiwan. Macrolide resistance was identified by mutations in domain V of MP 23S rRNA. Severe disease referred to symptoms warranting oxygen therapy, septic shock, or intensive care unit admission.ResultsAmong 495 LRTI patients, 195 (39.4%) had CAMP, of which 106 (54.4%) had concurrent serological evidence of MP infection. The diagnostic sensitivity of IgM in the acute phase was 65.6%. CAMP case numbers were highest from July 2019 to January 2020. The most common clinical presentations of CAMP were fever (99.0%), cough (99.0%), and coryza (31.8%). Despite a high rate of macrolide resistance (88.1%), macrolide-resistant MP (MRMP) did not differ from macrolide-sensitive MP (MSMP) in clinical course or severity. Delayed administration of effective antimicrobial treatment was also associated with severe disease (p < 0.05).ConclusionEarly diagnosis and determination of MRMP are needed for effective management of MP infection.     

Prevalence and characterization of extended-spectrum β-lactamase-producing clinical Salmonella enterica isolates in Dakar,Senegal, from 1999 to 2009

A total of 1623 clinical isolates of Salmonella belonging to 229 serotypes were received by the Senegalese Reference Center for Enterobacteria from January 1999 to December 2009. The most common serotypes were Enteritidis (19% of the isolates), Typhi (8%), Typhimurium (7%) and Kentucky (4%). A significant increase in the prevalence of resistance to amoxicillin (0.9% in 1999 to 11.1% in 2009) and nalidixic acid (0.9% in 1999 to 26.7% in 2009) was observed in non-typhoidal Salmonella serotypes. For critically important antibiotics, notably ciprofloxacin and extended-spectrum cephalosporins (ESCs), the rates of resistance were low: 0.3% and 0.5%, respectively. Seven ESC-resistant Salmonella strains and three additional ESC-resistant strains from Senegal (1990) and Mali (2007) were studied to identify the genetic basis of their antibiotic resistance. All ESC-resistant strains produced an extended-spectrum β-lactamase (ESBL). These were CTX-M-15 (n = 6; 2000–2008), SHV-12 (n = 3; 2000–2001) and SHV-2 (n = 1; 1990). A large IncHI2 ST1 pK29-like plasmid was found in six strains (three producing SHV-12 and three CTX-M-15), whereas IncN and IncF plasmids were found in three strains and one strain, respectively. The association of plasmid-mediated quinolone resistance (PMQR) genes qnrB1 and aac(6′)-Ib-cr was found in four ESBL-producing strains, leading to decreased susceptibility and even full resistance to ciprofloxacin (MIC range 0.75–2 mg/L) despite the absence of mutations in the quinolone resistance-determining region (QRDR) of gyrA, gyrB, parC and parE. This association of ESBL and multiple PMQR mechanisms within the same strains is therefore a serious concern as it hampers the use of both ESCs and fluoroquinolones for severe Salmonella infections.     

ELISA measurement of specific non-antigen-bound antibodies to Aβ1-42 monomer and soluble oligomers in sera from Alzheimer's disease, mild cognitively impaired, and noncognitively impaired subjects

Background

Neuroinflammation is an important contributor to the development of neurodegenerative diseases, including Alzheimer's disease. Thus, there is a keen interest in identifying compounds, especially from herbal sources, that can inhibit neuroinflammation. Amyloid-β (Aβ) is a major component of the amyloid plaques present in the brains of Alzheimer's disease patients. Here, we examined whether sinomenine, present in a Chinese medicinal plant, prevents oligomeric Aβ-induced microglial activation and confers protection against neurotoxicity.

Methods

Oligomeric amyloid-β was prepared from Aβ(1-42). Intracellular reactive oxygen species production was determined using the dye 2',7'-dichlorodihydrofluorescin diacetate. Nitric oxide level was assessed using the Griess reagent. Flow cytometry was used to examine the levels of inflammatory molecules. BV2-conditioned medium was used to treat hippocampal cell line (HT22) and primary hippocampal cells in indirect toxicity experiments. Toxicity was assessed using MTT reduction and TUNEL assays.

Results

We found that sinomenine prevents the oligomeric Aβ-induced increase in levels of reactive oxygen species and nitric oxide in BV2 microglial cells. In addition, sinomenine reduces levels of Aβ-induced inflammatory molecules. Furthermore, sinomenine protects hippocampal HT22 cells as well as primary hippocampal cells from indirect toxicity mediated by Aβ-treated microglial cells, but has no effect on Aβ-induced direct toxicity to HT22 cells. Finally, we found that conditioned medium from Aβ-treated BV2 cells contains increased levels of nitric oxide and inflammatory molecules, but the levels of these molecules are reduced by sinomenine.

Conclusions

Sinomenine prevents oligomeric Aβ-induced microglial activation, and confers protection against indirect neurotoxicity to hippocampal cells. These results raise the possibility that sinomenine may have therapeutic potential for the treatment of Alzheimer's diseases as well as other diseases that involve neuroinflammation.     

Human leukocyte antigen–A, -B, -C, -DRB1 allele and haplotype frequencies in Americans originating from southern Europe: Contrasting patterns of population differentiation between Italian and Spanish Americans

High-resolution DNA sequencing was used to identify the human leukocyte antigen (HLA) –A, -B, -C, and -DRB1 alleles found in 552 individuals from the United States indicating Southern European (Italian or Spanish) heritage. A total of 46 HLA-A, 80 HLA-B, 32 HLA-C, and 50 DRB1 alleles were identified. Frequent alleles included A*02:01:01G (allele frequency = 0.26 in Italian Americans and 0.22 in Spanish Americans); B*07:02:01G (Italian Americans allele frequency = 0.11); B*44:03 (Spanish Americans allele frequency = 0.07); C*04:01:01G and C*07:01:01G (allele frequency = 0.13 and 0.16, respectively, in Italian Americans; 0.15 and 0.12, respectively, in Spanish Americans); and DRB1*07:01:01 (allele frequency = 0.12 in each population). The action of balancing selection was inferred at the HLA-B and -C loci in both populations. The A*01:01:01G-C*07:01:01G-B*08:01:01G-DRB1*03:01:01 haplotype was the most frequent A-C-B-DRB1 haplotype in Italian Americans (haplotype frequency = 0.049), and was the second most frequent haplotype in Spanish Americans (haplotype frequency = 0.021). A*29:02:01-C*16:01:01-B*44:03-DRB1*07:01:01 was the most frequent A-C-B-DRB1 in Spanish Americans (haplotype frequency = 0.023), and was observed at a frequency of 0.015 in Italian Americans. Pairwise F′_st values measuring the degree of differentiation between these Southern European American populations as well as European and European American populations suggest that Spanish Americans constitute a distinct subset of the European American population, most similar to Mexican Americans, whereas Italian Americans cannot be distinguished from the larger European American population.     

Characteristics of rectal chlamydia among men who have sex with men in southern Taiwan, 2020–2022: An emerging threat of rectal lymphogranuloma venereum L2b

BackgroundThe prevalence of rectal chlamydia among men who have sex with men (MSM) without human deficiency virus infection (non-HIV) remains uncertain in Taiwan, and rectal lymphogranuloma venereum (LGV) among MSM has never been reported in the Far East.Material and methodsFrom January 2020 to April 2022, MSM coming for anonymous voluntary counseling and testing, for pre-exposure prophylaxis, and for antiretroviral therapy were enrolled. All participants submitted his fecal samples and completed a QR-code questionnaire. Medical records of those who took regular medical visits for HIV were recorded. Multiplex polymerase chain reaction (PCR) was performed for all fecal samples, and ompA gene sequencing was therefore performed for each Chlamydia-positive fecal sample.ResultsAmong 341 MSM during 2020–2022 in southern Taiwan, 21 (6.2%) had rectal chlamydia infection. Risk factors of rectal chlamydia included co-infection with rectal gonorrhea (adjusted odds ratio [AOR] 6.78, 95% confidence interval [CI] 1.44–31.91, P = 0.015) and multiple sexual partners (AOR 1.373, 95% CI 1.002–1.882, P = 0.048). Further ompA gene sequencing from 19 Chlamydia-positive fecal samples revealed that the prevalent genotypes or genovariants were Da (26.3%) and L2b (26.3%), followed by B (21.1%), J (14.3%), and G (9.5%). All cases of rectal LGV genovariant L2b presented as acute proctitis with diarrhea, anal pain, or discharge and were treated successfully with prolonged treatment of doxycycline.ConclusionsRectal gonorrhea and multiple sexual partners are risk factors for rectal chlamydia. Clinicians in Taiwan should be aware of the emerging threat of rectal LGV among MSM with acute proctitis.     

Comparative activity of plazomicin against extended-spectrum cephalosporin-resistant Escherichia coli clinical isolates (2012–2017) in relation to phylogenetic background,sequence type 131 subclones,blaCTX-M genotype,and resistance to comparator agents

Extended-spectrum cephalosporin-resistant Escherichia coli (ESCREC) are a growing threat. Leading ESCREC lineages include sequence type ST131, especially its (bla_CTX-M-15-associated) H30Rx subclone and (bla_CTX-M-27-associated) C1-M27 subset within the H30R1 subclone. The comparative activity against such strains of alternative antimicrobial agents, including the recently developed aminoglycoside plazomicin, is undefined, so was investigated here. We assessed plazomicin and 11 comparators for activity against 216 well-characterized ESCREC isolates (Minnesota, 2012–2017) and then compared broth microdilution MICs with phylogenetic and clonal background, beta-lactamase genotype (bla_CTX-M; group 1 and 9 variants), and co-resistance. Percent susceptible was > 99% for plazomicin, meropenem, imipenem, and tigecycline; 96–98% for amikacin and ertapenem; and ≤ 75% for the remaining comparators. For most comparators, MICs varied significantly in relation to multiple bacterial characteristics, in agent-specific patterns. By contrast, for plazomicin, the only bacterial characteristic significantly associated with MICs was ST131 subclone: plazomicin MICs were lowest among O16 ST131 isolates and highest among ST131-H30R1 C1-M27 subclone isolates. Additionally, plazomicin MICs varied significantly in relation to resistance vs. susceptibility to comparator agents only for amikacin and levofloxacin. For most study agents, antimicrobial activity against ESCREC varied extensively in relation to multiple bacterial characteristics, including clonal background, whereas for plazomicin, it varied only by ST131 subclone (C1-M27 isolates least susceptible, O16 isolates most susceptible). These findings support plazomicin as a reliable alternative for treating ESCREC infections and urge continued attention to the C1-M27 ST131 subclone.

     

Effects of water-soluble cigarette smoke extracts upon the release of β-hexosaminidase from RBL-2H3 basophilic leukaemia cells in response to substance P,compound 48/80, concanavalin A and antigen stimulation

Objective and design: To determine whether water-soluble constituents of cigarette smoke affect mast cell function using an in vitro model, RBL-2H3 basophilic leukaemia cells. Materials and methods: RBL-2H3 cells were induced to degranulate in response to compound 48/80 and substance P, as assessed by monitoring the release of the granular enzyme -hexosaminidase, by treatment for 7 days with 20 M quercetin. Responses to concanavalin A and antigen were determined by measuring the -hexosaminidase release from cells cultured on fibronectin-coated plates. Results: The -hexosaminidase release response to compound 48/80 induced by quercetin treatment was accompanied by a release of lactate dehydrogenase, suggesting that degranulation is not the only process triggered by compound 48/80 under these conditions. Quercetin treatment reduced the -hexosaminidase release response to concanavalin A. Precoating of the culture wells with rat fibronectin enhanced the -hexosaminidase response to calcimycin, but not to concanavalin A. Under these conditions, concanavalin A did not induce a release of lactate dehydrogenase. The responses to c48/80, substance P, calcimycin, concanavalin A and antigen (after IgE pretreatment) were reduced by treatment with cigarette smoke solution obtained from standard and low-tar cigarettes (IR3 and IR5F). The effect of cigarette smoke solution from IR5F cigarettes upon the -hexosaminidase release elicited by compound 48/80 (in quercetin-treated cells) and by concanavalin A (in cells cultured on fibronectin-coated wells) could be prevented by N-acetyl-L-cysteine, but not with either hemoglobin, -tocopherol, catalase or palmitoylethanolamide. N-acetyl-L-cysteine also reduced the effect of cigarette smoke solution upon the degranulation response to antigen. Conclusion: Under the conditions used, oxidants present in cigarette smoke solution from IR5F cigarettes reduce the ability of RBL-2H3 cells to degranulate in response to both immunological and non-immunological stimuli.Received 6 December 2002; returned for revision 1 April 2003; accepted by I. Ahnfelt-RøJune 2003     

Trends in the susceptibility of methicillin-resistant Staphylococcus aureus to nine antimicrobial agents,including ceftobiprole,nemonoxacin, and tyrothricin: results from the Tigecycline In Vitro Surveillance in Taiwan (TIST) study, 2006–2010

This study investigated the in vitro susceptibilities of methicillin-resistant Staphylococcus aureus (MRSA) to nine antimicrobial agents in Taiwan. A total of 1,725 isolates were obtained from 20 hospitals throughout Taiwan from 2006 to 2010. The minimum inhibitory concentrations (MICs) of the nine agents were determined by the agar dilution method. The MICs of mupirocin and tyrothricin were determined for 223 MRSA isolates collected from 2009 to 2010. For vancomycin, 99.7 % were susceptible; however, 30.0 % (n?=?517) exhibited MICs of 2 μg/ml and 0.3 % (n?=?6) demonstrated intermediate susceptibility (MICs of 4 μg/ml). Nearly all isolates (≥99.9 %) were susceptible to teicoplanin, linezolid, and daptomycin. The MIC₉₀ values were 2 μg/ml for ceftobiprole and 1 μg/ml for nemonoxacin. The MIC₉₀ values of mupirocin and tyrothricin were 0.12 and 4 μg/ml, respectively. MIC creep was noted for daptomycin during this period, but not for vancomycin, teicoplanin, linezolid, or tigecycline. For isolates with vancomycin MICs of 2 μg/ml, the MIC₉₀ values were 2 μg/ml for teicoplanin, 0.5 μg/ml for daptomycin, and 0.5 μg/ml for tigecycline. Those values were four- to eight-fold higher than those among isolates with vancomycin MICs of 0.5 μg/ml (2, 0.06, and 0.12 μg/ml, respectively). Of the nine MRSA isolates exhibiting non-susceptibility to vancomycin (n?=?6), teicoplanin (n?=?1), daptomycin (n?=?2), or tigecycline (n?=?1), all had different pulsotypes, indicating the absence of intra-hospital or inter-hospital spread. The presence of a high proportion of MRSA isolates with elevated MICs (2 μg/ml) and MIC creep of daptomycin might alert clinicians on the therapy for serious MRSA infections in Taiwan.     

In vitro activity of cefiderocol,cefepime/enmetazobactam,cefepime/zidebactam,eravacycline, omadacycline,and other comparative agents against carbapenem-non-susceptible Pseudomonas aeruginosa and Acinetobacter baumannii isolates associated from bloodstream infection in Taiwan between 2018–2020

Background/purposeThis study aimed to investigate the in vitro susceptibilities of carbapenem-non-susceptible Pseudomonas aeruginosa (CNSPA) and Acinetobacter baumannii (CNSAB) isolates to cefiderocol, novel β-lactamase inhibitor (BLI) combinations, new tetracycline analogues, and other comparative antibiotics.MethodsIn total, 405 non-duplicate bacteremic CNSPA (n = 150) and CNSAB (n = 255) isolates were collected from 16 hospitals in Taiwan between 2018 and 2020. Minimum inhibitory concentrations (MICs) were determined using the broth microdilution method, and susceptibilities were interpreted according to the relevant guidelines or in accordance with results of previous studies and non-species-related pharmacokinetic/pharmacodynamic data.ResultsAmong the isolates tested, cefiderocol demonstrated potent in vitro activity against CNSPA (MIC_50/90, 0.25/1 mg/L; 100% of isolates were inhibited at ≤4 mg/L) and CNSAB (MIC_50/90, 0.5/2 mg/L; 94.9% of isolates were inhibited at ≤4 mg/L) isolates. More than 80% of CNSPA isolates were susceptible to cefiderocol, ceftazidime/avibactam, ceftolozane/tazobactam, and amikacin, based on breakpoints established by the Clinical and Laboratory Standards Institute. Activities of new BLI combinations varied significantly. Tetracycline analogues, including tigecycline (MIC_50/90, 1/2 mg/L; 92.5% of CNSAB isolates were inhibited at ≤2 mg/L) and eravacycline (MIC_50/90, 0.5/1 mg/L; 99.6% of CNSAB isolates were inhibited at ≤2 mg/L) exhibited more potent in vitro activity against CNSAB than omadacycline (MIC_50/90, 4/8 mg/L).ConclusionsThe spread of CNSPA and CNSAB poses a major challenge to global health. Significant resistance be developed even before a novel agent becomes commercially available. The development of on-site antimicrobial susceptibility tests for these novel agents is of great clinical importance.     

A Cohort of 169 Chronic Granulomatous Disease Patients Exposed to BCG Vaccination: a Retrospective Study from a Single Center in Shanghai,China (2004–2017)

Purpose

Clinical diagnosis and treatment for chronic granulomatous disease (CGD) have advanced greatly in recent years. However, CGD patients in China have unique clinical features and infection spectrums, which are challenging to their caretakers. Here, we summarized the clinical characteristics, genetic features, treatment, and prognosis of CGD in a single center in Shanghai.

Methods

One hundred sixty-nine CGD patients were recruited between January 2004 and May 2017 based on clinical diagnosis. Electronic medical charts were reviewed to collect clinical data.

Results

Among the 169 patients recruited, CYBB mutations were identified in 150 cases, whereas CYBA mutations were identified in 7 cases, NCF1 in 5, and NCF2 in 7. The medium age at onset was 1 month (interquartile range 1–3). The medium age at diagnosis was 8 months (interquartile range 3–19). The most common infection sites were the lung (95.9%), lymph node (58.5%), skin (45.4%), intestinal (43.1%), and perianal (38.5%). Bacillus Calmette-Guérin (BCG) infections were common (59.2%). In addition, other non-infectious complications were also common, including anemia (55.4%) and impaired liver functions (34.6%). Thirty-one patients received stem cell transplantation. By the end of this study, 83/131 patients survived.

Conclusions

Similar to other non-consanguineous populations, X-linked CGD accounted for the majority of the cases in China. However, BCG infections were a clinical challenge unique to China. In addition, severe infections were the major cause of death and the overall mortality was still high in China.

     

Rotavirus infection in children of Nizhny Novgorod, Russia: the gradual change of the virus allele from P[8]-1 to P[8]-3 in the period 1984–2010

A collection of rotavirus samples collected over a 26-year period was examined to study the dynamics of change in RV strains of genotype P[8] in a geographically defined population (Nizhny Novgorod, Russia; children under 6?years) with no vaccine pressure. Phylogenetic analysis of gene VP4 (subunit VP8*) showed the presence of two lines of genotype P[8]: P[8]-1 and P[8]-3. Since 1997, the dominant population of rotavirus has been occupied by strains carrying the allele P[8]-3, which is associated with G1, G3 and G4. The complete replacement of the allele P[8]-1 to P[8]-3 took 19 epidemic years.     

Distribution of <Emphasis Type="Italic">Legionella pneumophila</Emphasis> serogroups,monoclonal antibody subgroups and DNA sequence types in recent clinical and environmental isolates from England and Wales (2000–2008)

Clinical isolates of Legionella pneumophila, obtained from 167 patients, who acquired their illness in the community in England and Wales between January 2000 and March 2008, were compared with 276 environmental isolates of L. pneumophila obtained over the same period as part of the routine sampling of ‘managed’ water systems. The 443 isolates were typed by monoclonal antibody (mAb) subgrouping and the internationally standardised, seven-gene loci, sequence-based typing (SBT) scheme of the European Working Group for Legionella Infections (EWGLI). Of the clinical isolates, 97.6% were L. pneumophila serogroup (sgp) 1, compared with only 55.8% of environmental isolates (P = 0.0002); 91.6% were subgrouped as mAb3/1+ve, compared with only 8.3% of environmental isolates (P < 0.0001). The isolates were very diverse, with SBT identifying 111 sequence types (STs) (index of diversity [IOD] 0.954). Among the clinical isolates, 42 ST were seen, with one (ST47) accounting for 25.7% and three (ST47, ST37 and ST62) accounting for 46.1% of all isolates. Eighty-two STs were identified among the environmental isolates, with two (ST1 and ST79) accounting for 34.1% of these. Comparison of the STs seen among clinical and environmental isolates showed that there was very little overlap between the two populations (P < 0.0001), with common clinical strains found in the environment very infrequently: 0.4, 0.7 and 0% (ST47, ST37 and ST62, respectively), and common environmental strains rarely causing disease: 4.8 and 1.2% (ST1 and ST79, respectively). Combining phenotypic and genotypic data identified 144 phenons (IOD 0.970); 52 among clinical isolates and 101 among environmental isolates. The most abundant clinical strain, mAb ‘Allentown’ ST47, accounted for 22.8% of cases, but was only found once in the environment. Conversely, mAb ‘Oxford/OLDA’ ST1 was the most common environmental strain (17.0%), but only caused two infections. A review of the published data shows that mAb ‘Allentown’ ST47 is also an important cause of infection in France and possibly in the Netherlands. However, it was not found in a large study of German clinical isolates. This study confirms previous work showing that just a few strains of L. pneumophila cause the majority of community-acquired Legionella infection in England and Wales, and that these clinically significant strains are only rarely found in managed water systems. These data suggest that knowing which particular strain is present in an environment might be at least as important as knowing the quantity in which legionellae are present.

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