Do Commonly Used Antimicrobial Topicals Facilitate Venous Leg Ulcer Healing?

OBJECTIVE: To survey which topical antimicrobials are most helpful in treating venous leg ulcers (VLUs). DATA SOURCES: In this narrative review, the authors searched the databases of Google Scholar, Cochrane Library, and Wiley Online Library. STUDY SELECTION: Studies were eligible for inclusion if they studied the effects of antimicrobial agents on chronic VLU healing and were published after 1985. Exceptions to this were in vitro studies of manuka honey and Dakin solution (Century Pharmaceuticals). Search terms included "venous leg ulcer", "nonhealing ulcer", "antimicrobial resistance", and "biofilms". DATA EXTRACTION: Data extracted included design, setting, descriptions of intervention and control groups, outcomes, data collection tools, and potential harms. DATA SYNTHESIS: A total of 19 articles encompassing 26 studies/trials met the inclusion criteria. Of the 26 studies, 17 were randomized controlled trials; the remaining 9 were a mix of lower-quality case series and comparative, nonrandomized, or retrospective studies. CONCLUSION: Studies suggest that VLUs can be treated with multiple different topical antimicrobials. Depending on the extent of chronicity and bacterial colonization, some antimicrobials may be better suited than others.

The Clinical Utility of Two High-Throughput 16S rRNA Gene Sequencing Workflows for Taxonomic Assignment of Unidentifiable Bacterial Pathogens in Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry.

Bacterial pathogens that cannot be identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) are occasionally encountered in clinical laboratories. The 16S rRNA gene is often used for sequence-based analysis to identify these bacterial species. Nevertheless, traditional Sanger sequencing is laborious, time-consuming, and low throughput. Here, we compared two commercially available 16S rRNA gene sequencing tests that are based on Illumina and Nanopore sequencing technologies, respectively, in their ability to identify the species of 172 clinical isolates that failed to be identified by MALDI-TOF MS. Sequencing data were analyzed by the respective built-in programs (MiSeq Reporter software of Illumina and Epi2me of Nanopore) and BLAST+ (v2.11.0). Their agreement with Sanger sequencing on species-level identification was determined. Discrepancies were resolved by whole-genome sequencing. The diagnostic accuracy of each workflow was determined using the composite sequencing result as the reference standard. Despite the high base-calling accuracy of Illumina sequencing, we demonstrated that the Nanopore workflow had a higher taxonomic resolution at the species level. Using built-in analysis algorithms, the concordance of Sanger 16S with the Illumina and Nanopore workflows was 33.14% and 87.79%, respectively. The agreement was 65.70% and 83.14%, respectively, when BLAST+ was used for analysis. Compared with the reference standard, the diagnostic accuracy of Nanopore 16S was 96.36%, which was identical to that of Sanger 16S and better than that of Illumina 16S (69.07%). The turnaround time of the Illumina workflow and the Nanopore workflow was 78 h and 8.25 h, respectively. The per-sample cost of the Illumina and Nanopore workflows was US$28.5 and US$17.7, respectively.

Regulation of T helper cell responses during antigen presentation by norepinephrine-exposed endothelial cells.

Dermal blood vessels and regional lymph nodes are innervated by sympathetic nerves and, under stress, sympathetic nerves release norepinephrine (NE). Exposure of primary murine dermal microvascular endothelial cells (pDMECs) to NE followed by co-culture with Langerhans cells (LCs), responsive CD4+ T-cells and antigen resulted in modulation of CD4+ T-cell responses. NE-treatment of pDMECs induced increased production of interleukin (IL)-6 and IL-17A while down-regulating interferon (IFN)-γ and IL-22 release. This effect did not require contact between pDMECs and LCs or T-cells and depended upon pDMEC production of IL-6. The presence of NE-treated pDMECs increased the proportion of CD4+ T-cells expressing intracellular IL-17A and increased IL-17A mRNA while decreasing the proportion of IFN-γ- or IL-22-expressing CD4+ T-cells and mRNA levels for those cytokines. Retinoic acid receptor-related orphan receptor gamma (ROR-γt) mRNA was significantly increased in CD4+ T-cells while T-box transcription factor (T-bet) mRNA was decreased. Intradermal administration of NE prior to hapten immunization at the injection site produced a similar bias in draining lymph node CD4+ T-cells towards IL-17A and away from IFN-γ and IL-22 production. Under stress, release of NE may have significant regulatory effects on the outcome of antigen presentation through actions on ECs with enhancement of inflammatory skin disorders involving IL-17/T helper type 17 (Th17) cells.

Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition.

BACKGROUND: Prostate-specific antigen (PSA) and PSA-velocity (PSAV) have been used to identify men at risk of prostate cancer (PrCa). The IMPACT study is evaluating PSA screening in men with a known genetic predisposition to PrCa due to BRCA1/2 mutations. This analysis evaluates the utility of PSA and PSAV for identifying PrCa and high-grade disease in this cohort. METHODS: PSAV was calculated using logistic regression to determine if PSA or PSAV predicted the result of prostate biopsy (PB) in men with elevated PSA values. Cox regression was used to determine whether PSA or PSAV predicted PSA elevation in men with low PSAs. Interaction terms were included in the models to determine whether BRCA status influenced the predictiveness of PSA or PSAV. RESULTS: 1634 participants had ⩾3 PSA readings of whom 174 underwent PB and 45 PrCas diagnosed. In men with PSA >3.0 ng ml-l, PSAV was not significantly associated with presence of cancer or high-grade disease. PSAV did not add to PSA for predicting time to an elevated PSA. When comparing BRCA1/2 carriers to non-carriers, we found a significant interaction between BRCA status and last PSA before biopsy (P=0.031) and BRCA2 status and PSAV (P=0.024). However, PSAV was not predictive of biopsy outcome in BRCA2 carriers. CONCLUSIONS: PSA is more strongly predictive of PrCa in BRCA carriers than non-carriers. We did not find evidence that PSAV aids decision-making for BRCA carriers over absolute PSA value alone.

Prostate-specific antigen velocity in a prospective prostate cancer screening study of men with genetic predisposition.

This corrects the article DOI: 10.1038/bjc.2017.429.

Artificial ventilation during transport: A randomized crossover study of manual resuscitators with comparison to mechanical ventilators in a simulation model.

BACKGROUND: Positive-pressure ventilation in critically ill patients is commonly administered via a manual resuscitation device or a mechanical ventilator during transport. Our group previously compared delivered ventilation parameters between a self-inflating resuscitator and a flow-inflating resuscitator during simulated in-hospital pediatric transport. However, unequal group access to inline pressure manometry may have biased our results. In this study, we examined the performance of the self-inflating resuscitator and the flow-inflating resuscitator, both equipped with inline manometry, and several mechanical ventilators to deliver prescribed ventilation parameters during simulated pediatric transport. METHODS: Thirty anesthesia providers were randomized to initial resuscitator device used to hand ventilate a test lung. The resuscitators studied were a Jackson-Rees circuit (flow-inflating resuscitator) or a Laerdal pediatric silicone resuscitator (self-inflating resuscitator), both employing manometers. The scenario was repeated using several mechanical transport ventilators (Hamilton-T1, LTV® 1000, and LTV® 1200). The primary outcome was the proportion of total breaths delivered within the predefined target PIP/PEEP range (30 ± 3, 10 ± 3 cm H2 O). RESULTS: The Hamilton-T1 outperformed the other ventilators for breaths in the recommended range (χ2  = 2284, df = 2, P < .001) and with no breaths in the unacceptable range (χ2  = 2333, df = 2, P < .001). Hamilton-T1 also outperformed all human providers in proportion of delivered acceptable and unacceptable breaths (χ2  = 4540, df = 3, P < .001 and χ2  = 639, df = 3, P < .001, respectively). Compared with the flow-inflating resuscitator, the self-inflating resuscitator was associated with greater odds of breaths falling outside the recommended range (Odds ratio (95% CI): 1.81 (1.51-2.17)) or unacceptable (Odds ratio (95% CI): 1.63 (1.48-1.81)). CONCLUSION: This study demonstrates that a majority of breaths delivered by manual resuscitation device fall outside of target range regardless of provider experience or device type. The mechanical ventilator (Hamilton-T1) outperforms the other positive-pressure ventilation methods with respect to delivery of important ventilation parameters. In contrast, 100% of breaths delivered by the LTV 1200 were deemed unacceptable.

Extended use of perioperative antibiotics in head and neck microvascular reconstruction.

PURPOSE: Many head and neck surgical procedures are considered clean-contaminated wounds and antibiotic prophylaxis is recommended. Despite prophylaxis, the incidence of surgical site infections remains significant - especially in the setting of free tissue transfer. The antibiotic course is often of a longer duration after free tissue transfer than the recommended 24hour post-operatively. Currently, there is no consensus on appropriate antibiotic regimen or duration at this time. This study investigates the outcomes of a 7-day perioperative antibiotic regimen after microvascular reconstruction of the head and neck at our institution. MATERIALS AND METHODS: A retrospective review was performed of 72 patients undergoing microvascular free tissue at our institution between 09/2011 and 03/2014. The antibiotic regimen, post-operative surgical (including surgical site infections) and medical complications were noted. Our rates of complications and adverse events were compared to all surgical patients, as well as all inpatients hospital-wide with use of the University Health System Consortium database. RESULTS: Seventy-two subjects met inclusion criteria for this study. The majority of subjects received cefazolin/metronidazole (69.4%). Subjects with beta-lactam allergy received clindamycin (12.5%). The remainder received an alternative regimen (18.1%). All received at least 7days of antibiotics. The rate of hospital acquired C. difficile diarrhea was 0.57% hospital-wide, 1.13% in Otolaryngology patients, and 1.4% in this study. There were no instances of a multi-drug resistant infection or any adverse reactions to the administration of antibiotics. When compared with other antibiotic regimens, clindamycin was associated with a significantly increased rate of either medical or surgical infections (OR 14.38, p=0.02) and longer hospital stay (average=18days, p<0.05). CONCLUSION: The use of a 7-day prophylactic antibiotic regimen is not associated with an increased risk of antibiotic-associated infections, multi-drug resistant infections, or antibiotic-associated complications. The use of clindamycin is associated with increased risk of medical and surgical infections post-operatively and should be avoided in the prophylactic perioperative phase after free tissue transfer of the head and neck.

Inflamed actinic keratoses associated with pemetrexed and carboplatin therapy.

Eruptive actinic keratosis (AK) consequent to systemic chemotherapy can be confused with drug allergies. We present the first case of inflamed AKs in one patient after receiving combination therapy with pemetrexed and carboplatin.A 68-year-old woman with non-small cell lung adenocarcinoma (NSCLC) presented with numerous pruritic ill-defined, gritty, erythematous papules consistent with AKs on her upper chest, upper back, and arms two weeks after completing the first cycle of combination therapy with carboplatin and pemetrexed. The care team managed her with topical steroids and the lesions resolved within one month. The patient resumed the second cycle of chemotherapy and reported the occurrence of a similar but milder eruption.This case illustrates that eruptive AKs should be considered in the differential diagnosis of drug-related rashes, especially if the physical exam is suggestive. The mainstay of treatment should be directed at symptomatic improvement, and chemotherapy may be continued.

Gordonia hongkongensis sp. nov., isolated from blood culture and peritoneal dialysis effluent of patients in Hong Kong.

Two bacterial strains, HKU50T and HKU46, were isolated in Hong Kong from the blood culture and the peritoneal dialysis effluent of two patients. The strains are Gram-stain-positive, acid-fast, non-motile, non-sporulating bacilli. They grow on Columbia agar with 5 % defibrinated sheep blood and brain-heart infusion agar under aerobic conditions with 5 % CO2 at 37 °C as pink-to-orange, non-haemolytic colonies. The strains are catalase-positive and oxidase-negative, and have a unique biochemical profile distinguishable from other closely related species. DNA sequencing revealed that both isolates possessed multiple intra-genomic 16S rRNA gene copies (99.8-100 % sequence identities to Gordonia lacunae NRRL B-24551T and Gordonia terrae NRRL B-16283T). Phylogenetic analysis of the 16S rRNA gene, secA1 and gyrB showed that the two isolates formed a distinct branch within the genus Gordonia and were most closely related to G. lacunae and G. terrae. DNA-DNA hybridization demonstrated ≤53.7 % and ≤49.4 % DNA relatedness between the two isolates and G. lacunae, and between the two isolates and G. terrae, respectively. Hierarchical cluster analysis of MALDI-TOF MS main spectrum profiles showed that strains HKU50T and HKU46 were closely related to each other, but were distinct from G. lacunae, G. terrae, or any other species of the genus Gordonia in the Bruker database. The chemotaxonomic traits of the two strains were highly similar, and the major fatty acids were summed feature 4 (iso-C15 : 0 2-OH/C16 : 1trans-9), C16 : 0, C18 : 1cis-9, and tuberculostearic acid. A novel species named Gordonia hongkongensis sp. nov. is proposed to accommodate strains HKU50T and HKU46, with strain HKU50T (=CCOS 955T=CIP 111027T=NBRC 111234T=NCCP 16210T) as the type strain.

High recurrence rate supports need for secondary prophylaxis in non-HIV patients with disseminated mycobacterium avium complex infection: a multi-center observational study.

BACKGROUND: Long-term outcomes in non-HIV immunocompromised patients with disseminated Mycobacterium avium complex (dMAC) infections are unknown and the need for post-treatment secondary prophylaxis against MAC is uncertain in this setting. The objective of this study was to determine the need of continuing secondary anti-MAC prophylaxis in non-HIV patients after completing treatment of the primary dMAC episode. METHODS: We conducted a ten-year multi-center analysis of non-HIV immunosuppressed patients with dMAC infections in Hong Kong. RESULTS: We observed sixteen patients with dMAC during the study period of which five (31 %) were non-HIV immunosuppressed patients. In the non-HIV immunosuppressed group, three patients completed a treatment course without secondary prophylaxis, one patient received azithromycin-based secondary prophylaxis and one patient was still receiving therapy for the first dMAC episode. All the three patients who completed treatment without being given secondary prophylaxis developed recurrent dMAC infection requiring retreatment. CONCLUSIONS: In view of the high rate of dMAC infection recurrence in non-HIV immunocompromised patients following treatment completion, our data support long-term anti-MAC suppression therapy after treatment of the first dMAC infection episode in immunocompromised non-HIV patients, as is recommended for patients with advanced HIV. Tests of cell mediated immune function need to be evaluated to guide prophylaxis discontinuation in non-HIV patients.

Gordonia species as emerging causes of continuous-ambulatory-peritoneal-dialysis-related peritonitis identified by 16S rRNA and secA1 gene sequencing and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS).

We report here four cases of continuous ambulatory peritoneal dialysis-related peritonitis caused by three different species of Gordonia. The portal of entry was likely through Tenckhoff catheters. 16S rRNA and secA1 gene sequencing are so far the most reliable methods for the accurate identification of Gordonia species.

Transmission Patterns of Co-Circulation of Omicron Sub-Lineages in Hong Kong SAR, China, a City with Rigorous Social Distancing Measures, in 2022.

OBJECTIVE: This study aimed to characterize the changing landscape of circulating SARS-CoV-2 lineages in the local community of Hong Kong throughout 2022. We examined how adjustments to quarantine arrangements influenced the transmission pattern of Omicron variants in a city with relatively rigorous social distancing measures at that time. METHODS: In 2022, a total of 4684 local SARS-CoV-2 genomes were sequenced using the Oxford Nanopore GridION sequencer. SARS-CoV-2 consensus genomes were generated by MAFFT, and the maximum likelihood phylogeny of these genomes was determined using IQ-TREE. The dynamic changes in lineages were depicted in a time tree created by Nextstrain. Statistical analysis was conducted to assess the correlation between changes in the number of lineages and adjustments to quarantine arrangements. RESULTS: By the end of 2022, a total of 83 SARS-CoV-2 lineages were identified in the community. The increase in the number of new lineages was significantly associated with the relaxation of quarantine arrangements (One-way ANOVA, F(5, 47) = 18.233, p < 0.001)). Over time, Omicron BA.5 sub-lineages replaced BA.2.2 and became the predominant Omicron variants in Hong Kong. The influx of new lineages reshaped the dynamics of Omicron variants in the community without fluctuating the death rate and hospitalization rate (One-way ANOVA, F(5, 47) = 2.037, p = 0.091). CONCLUSION: This study revealed that even with an extended mandatory quarantine period for incoming travelers, it may not be feasible to completely prevent the introduction and subsequent community spread of highly contagious Omicron variants. Ongoing molecular surveillance of COVID-19 remains essential to monitor the emergence of new recombinant variants.

The clinical utility of Nanopore 16S rRNA gene sequencing for direct bacterial identification in normally sterile body fluids.

The prolonged incubation period of traditional culture methods leads to a delay in diagnosing invasive infections. Nanopore 16S rRNA gene sequencing (Nanopore 16S) offers a potential rapid diagnostic approach for directly identifying bacteria in infected body fluids. To evaluate the clinical utility of Nanopore 16S, we conducted a study involving the collection and sequencing of 128 monomicrobial samples, 65 polymicrobial samples, and 20 culture-negative body fluids. To minimize classification bias, taxonomic classification was performed using 3 analysis pipelines: Epi2me, Emu, and NanoCLUST. The result was compared to the culture references. The limit of detection of Nanopore 16S was also determined using simulated bacteremic blood samples. Among the three classifiers, Emu demonstrated the highest concordance with the culture results. It correctly identified the taxon of 125 (97.7%) of the 128 monomicrobial samples, compared to 109 (85.2%) for Epi2me and 102 (79.7%) for NanoCLUST. For the 230 cultured species in the 65 polymicrobial samples, Emu correctly identified 188 (81.7%) cultured species, compared to 174 (75.7%) for Epi2me and 125 (54.3%) for NanoCLUST. Through ROC analysis on the monomicrobial samples, we determined a threshold of relative abundance at 0.058 for distinguishing potential pathogens from background in Nanopore 16S. Applying this threshold resulted in the identification of 107 (83.6%), 117 (91.4%), and 114 (91.2%) correctly detected samples for Epi2me, Emu, and NanoCLUST, respectively, in the monomicrobial samples. Nanopore 16S coupled with Epi2me could provide preliminary results within 6 h. However, the ROC analysis of polymicrobial samples exhibited a random-like performance, making it difficult to establish a threshold. The overall limit of detection for Nanopore 16S was found to be about 90 CFU/ml.

Supravenous Repigmentation of Hair Shafts in a Patient with Regrowing Alopecia Totalis: A Case Report and Hypothesis.

Introduction: Alopecia areata (AA) is a type of nonscarring alopecia that has autoimmune etiology, in which the hair follicle, usually an immune-privileged site, becomes the target of attack. Alopecia totalis (AT) is a subset of AA in which patients completely lose hair on the scalp. Initial hair regrowth is often fine and without pigment. We present a case of AT in which pigmented hair grew only overlying superficial veins, a finding which has not been previously reported. Case Presentation: An adult female with brown hair presented with AA that progressed to AT despite the use of triamcinolone ointment and topical 2% tofacitinib ointment. She was treated with nightly augmented betamethasone dipropionate 0.05% ointment under occlusion. Two months later, she noticed diffuse regrowth of thin hair on her scalp, most of which was depigmented. However, linear bands of darkly pigmented hairs were noted overlying superficial scalp veins. Discussion/Conclusion: Loss of pigmentation and subsequent repigmentation of the hair shaft in regrowing AA is not entirely understood. Initial hair regrowth in AA tends to be fine and depigmented, although the hair will usually regain normal texture and color. Pigmentation following a vein suggests that local temperature may play a role, possibly augmented by corticosteroid induced reduced expression of inflammatory cytokines and endothelial release of the vasoconstrictor hormone endothelin, which stimulates melanogenesis.

Within-subjects vs between-subjects co-variation of prepulse-elicited reaction and the diminution of startle to the succeeding pulse stimulus in the prepulse inhibition paradigm.

Prepulse inhibition (PPI) refers to the diminution of the startle reflex to a sudden and intense acoustic stimulus (pulse) when this startle-eliciting pulse is preceded shortly by a weaker prepulse stimulus. PPI is widely used in evaluating the effects of psychomimetic and antipsychotic drugs on sensorimotor gating, but individual differences in PPI expression have received scant attention. We have previously shown that mice and rats exhibiting stronger motor response to the prepulse also exhibit more PPI. It remains unexplored, however, if this between-subjects correlation may be similarly observed across trials from a within-subjects perspective. Here, we mapped the prepulse-elicited response to the diminution of the startle response to the succeeding pulse stimulus, trial-by-trial, across nine prepulse-pulse definitions with varying prepulse and pulse intensities. The resulting within-subjects correlation independently obtained in 113 adult C57BL6 mice revealed that trials registering a stronger prepulse reaction also recorded a larger startle response to the pulse stimulus, indicative of weaker PPI, especially when higher-intensity prepulses were paired with low-intensity pulses. The within- and between-subjects analyses have apparently yielded two contrasting relationships between the direct motor response to the prepulse and the inhibition of subsequent startle reaction induced by the same prepulse. One interpretation is that the within-subjects correlation reflects state-dependent variation, whereas the between-subjects correlation stems from trait-dependent individual variation. Finally, whether our present findings may depend on the nature of the prepulse reaction is further discussed.

Aerosol transmission of SARS-CoV-2 due to the chimney effect in two high-rise housing drainage stacks.

Stack aerosols are generated within vertical building drainage stacks during the discharge of wastewater containing feces and exhaled mucus from toilets and washbasins. Fifteen stack aerosol-related outbreaks of coronavirus disease 2019 (COVID-19) in high-rise buildings have been observed in Hong Kong and Guangzhou. Currently, we investigated two such outbreaks of COVID-19 in Hong Kong, identified the probable role of chimney effect-induced airflow in a building drainage system in the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We injected tracer gas (SF6) into the drainage stacks via the water closet of the index case and monitored tracer gas concentrations in the bathrooms and along the facades of infected and non-infected flats and in roof vents. The air temperature, humidity, and pressure in vertical stacks were also monitored. The measured tracer gas distribution agreed with the observed distribution of the infected cases. Phylogenetic analysis of the SARS-CoV-2 genome sequences demonstrated clonal spread from a point source in cases along the same vertical column. The stack air pressure and temperature distributions suggested that stack aerosols can spread to indoors through pipe leaks which provide direct evidence for the long-range aerosol transmission of SARS-CoV-2 through drainage pipes via the chimney effect.

A low-cost TaqMan minor groove binder probe-based one-step RT-qPCR assay for rapid identification of N501Y variants of SARS-CoV-2.

The increasing prevalence of N501Y variants of SARS-CoV-2 has kindled global concern due to their enhanced transmissibility. Genome sequencing is the gold standard method to identify the emerging variants of concern. But it is time-consuming and expensive, limiting the widespread deployment of genome surveillance in some countries. Health authorities surge the development of alternative assay to expand screening capacity with reduced time and cost. In this study, we developed an in-house TaqMan minor groove binder (MGB) probe-based one-step RT-qPCR assay to detect the presence of N501Y mutation in SARS-CoV-2. A total of 168 SARS-CoV-2 positive respiratory specimens were collected to determine diagnostic accuracy of the RT-qPCR assay. As a reference standard, PANGO lineages and the mutation patterns of all samples were characterised by whole-genome sequencing. The analytical sensitivity and the ability of the assay to detect low frequency of N501Y variants were also evaluated. A total of 31 PANGO lineages were identified from 168 SARS-CoV-2 positive cases, in which 34 samples belonged to N501Y variants, including B.1.1.7 (n = 20), B.1.351 (n = 12) and P.3 (n = 2). The N501Y RT-qPCR correctly identified all 34 samples as N501Y-positive and the other 134 samples as wildtype. The limit-of-detection of the assay consistently achieved 1.5 copies/µL on four different qPCR platforms. N501Y mutation was successfully detected at an allele frequency as low as 10 % in a sample with mixed SARS-CoV-2 lineage. The N501Y RT-qPCR is simple and inexpensive (US$1.6 per sample). It enables robust high-throughput screening for surveillance of SARS-CoV-2 variants of concern harbouring N501Y mutation.

Knockout of the murine cysteine dioxygenase gene results in severe impairment in ability to synthesize taurine and an increased catabolism of cysteine to hydrogen sulfide.

Cysteine homeostasis is dependent on the regulation of cysteine dioxygenase (CDO) in response to changes in sulfur amino acid intake. CDO oxidizes cysteine to cysteinesulfinate, which is further metabolized to either taurine or to pyruvate plus sulfate. To gain insight into the physiological function of CDO and the consequence of a loss of CDO activity, mice carrying a null CDO allele (CDO(+/-) mice) were crossed to generate CDO(-/-), CDO(+/-), and CDO(+/+) mice. CDO(-/-) mice exhibited postnatal mortality, growth deficit, and connective tissue pathology. CDO(-/-) mice had extremely low taurine levels and somewhat elevated cysteine levels, consistent with the lack of flux through CDO-dependent catabolic pathways. However, plasma sulfate levels were slightly higher in CDO(-/-) mice than in CDO(+/-) or CDO(+/+) mice, and tissue levels of acid-labile sulfide were elevated, indicating an increase in cysteine catabolism by cysteine desulfhydration pathways. Null mice had lower hepatic cytochrome c oxidase levels, suggesting impaired electron transport capacity. Supplementation of mice with taurine improved survival of male pups but otherwise had little effect on the phenotype of the CDO(-/-) mice. H(2)S has been identified as an important gaseous signaling molecule as well as a toxicant, and pathology may be due to dysregulation of H(2)S production. Control of cysteine levels by regulation of CDO may be necessary to maintain low H(2)S/sulfane sulfur levels and facilitate the use of H(2)S as a signaling molecule.

Three cases of severe invasive infections caused by Campylobacter rectus and first report of fatal C. rectus infection.

We report the first fatal case of Campylobacter rectus infection due to a subdural empyema and ruptured mycotic intracranial aneurysm and two cases of limb-threatening C. rectus necrotizing soft tissue and bone infection and empyema thoracis that responded to amoxicillin-clavulanate and surgical debridement and drainage. All three strains were identified by 16S rRNA sequencing.