Radiological hip shape and patient-reported outcome measures in healed Perthes' disease.

Aims: This study aimed to evaluate the relationship between hip shape and mid-term function in Perthes' disease. It also explored whether the modified three-group Stulberg classification can offer similar prognostic information to the five-group system. Methods: A total of 136 individuals aged 12 years or older who had Perthes' disease in childhood completed the Patient-Reported Outcomes Measurement Information System (PROMIS) Mobility score (function), Nonarthritic Hip Score (NAHS) (function), EuroQol five-dimension five-level questionnaire (EQ-5D-5L) score (quality of life), and the numeric rating scale for pain (NRS). The Stulberg class of the participants' hip radiographs were evaluated by three fellowship-trained paediatric orthopaedic surgeons. Hip shape and Stulberg class were compared to PROM scores. Results: A spherical hip was associated with the highest function and quality of life, and lowest pain. Conversely, aspherical hips exhibited the lowest functional scores and highest pain. The association between worsening Stulberg class (i.e. greater deviation from sphericity) and worse outcome persisted after adjustment for age and sex in relation to PROMIS (predicted mean difference -1.77 (95% confidence interval (CI) -2.70 to -0.83)), NAHS (-5.68 (95% CI -8.45 to -2.90)), and NRS (0.61 (95% CI 0.14 to 1.08)), but not EQ-5D-5L (-0.03 (95% CI -0.72 to 0.11)). Conclusion: Patient-reported outcomes identify lower function, quality of life, and higher pain in aspherical hips. The magnitude of symptoms deteriorated with time. Hip sphericity (i.e. the modified three-group classification of spherical, oval, and aspherical) appeared to offer similar levels of detail to the five-group Stulberg classification.

Use of the PROMIS Mobility score in assessing function in adolescents and adults previously affected by childhood hip disease.

AIMS: The Patient-Reported Outcomes Measurement Information System (PROMIS) has demonstrated faster administration, lower burden of data capture and reduced floor and ceiling effects compared to traditional Patient Reported Outcomes Measurements (PROMs). We investigated the suitability of PROMIS Mobility score in assessing physical function in the sequelae of childhood hip disease. METHODS: In all, 266 adolscents (aged ≥ 12 years) and adults were identified with a prior diagnosis of childhood hip disease (either Perthes' disease (n = 232 (87.2%)) or Slipped Capital Femoral Epiphysis (n = 34 (12.8%)) with a mean age of 27.73 years (SD 12.24). Participants completed the PROMIS Mobility Computer Adaptive Test, the Non-Arthritic Hip Score (NAHS), EuroQol five-dimension five-level questionnaire, and the Numeric Pain Rating Scale. We investigated the correlation between the PROMIS Mobility and other tools to assess use in this population and any clustering of outcome scores. RESULTS: There was a strong correlation between the PROMIS Mobility and other established PROMs; NAHS (rs = 0.79; p < 0.001). There was notable clustering in PROMIS at the upper end of the distribution score (42.5%), with less seen in the NAHS (20.3%). However, the clustering was broadly similar between PROMIS Mobility and the comparable domains of the NAHS; function (53.6%), and activity (35.0%). CONCLUSION: PROMIS Mobility strongly correlated with other tools demonstrating convergent construct validity. There was clustering of physical function scores at the upper end of the distributions, which may reflect truncation of the data caused by participants having excellent outcomes. There were elements of disease not captured within PROMIS Mobility alone, and difficulties in differentiating those with the highest levels of function. Cite this article: Bone Jt Open 2021;2(12):1089-1095.

Modulation of JNK-1/ ß-catenin signaling by Lactobacillus casei, inulin and their combination in 1,2-dimethylhydrazine-induced colon cancer in mice.

Colon cancer is a complex disease that involves numerous genetic alterations that change the normal colonic mucosa into invasive adenocarcinoma. In the current study, the protective effects of inulin (prebiotic), Lactobacillus casei (L. casei, probiotic) and their combination (synbiotic) on 1,2-dimethylhydrazine (DMH)-induced colon cancer in male Swiss mice were evaluated. Animals were divided into: Control group, DMH-treated group, DMH plus inulin, DMH plus L. casei and DMH plus inulin plus L. casei-treated groups. Fecal microbiome analysis, biochemical measurements, histopathological examination of the colon tissues, immunostaining and Western blotting analysis of ß-catenin, GSK3ß and JNK-1 were performed. The prebiotic-, probiotic- and synbiotic-treated groups showed decreased levels of carcinoembryonic antigen and a lower number of aberrant crypt foci compared to the DMH-treated group with the synbiotic group exhibiting a superior effect. Furthermore, all treatments showed a body weight-reducing effect. Administration of inulin, L. casei or their combination increased the expression level of phospho-JNK-1 while they decreased the expression level of ß-catenin and phospho-GSK3ß. Remarkably, L. casei treatment resulted in enrichment of certain beneficial bacterial genera i.e. Akkermansia and Turicibacter. Therefore, administration of L. casei and inulin as a synbiotic combination protects against colon cancer in mice.

Cellular changes of the colon after mechanical bowel preparation.

BACKGROUND: The purpose of this study was to evaluate the effect of mechanical bowel preparation (MBP) on the intracellular environment, specifically evaluating butyrate transport, within the colon of the Sprague-Dawley rat. METHODS: Sixty-eight Sprague-Dawley rats were randomized to either an MBP group (n = 34) or a control group (n = 34). Twenty-four hours after the completion of the MBP, both groups were euthanized, and the colons were harvested. The level of cellular apoptosis was investigated after DNA fragmentation, poly(ADP-ribose) polymerase cleavage, and caspase assays. Western blot analysis was performed to measure the expression of the butyrate transporter protein, monocarboxylate transporters 1, and proliferating cell nuclear antigen (a marker for tissue proliferation). Immunohistochemical staining was performed to further investigate cellular proliferation. Statistical significance (P < 0.05) was determined using two-tailed t-test. RESULTS: Apoptosis was detected without significant differences in both groups. Western Blot analysis demonstrated that the expression of the monocarboxylate transporters 1 protein is downregulated in the MBP group (10.18 ± 3.09) compared with the control group (16.73 ± 7.39, P = 0.001), and proliferating cell nuclear antigen levels showed a decrease in cellular proliferation in the MBP group (13.35 ± 5.88) compared with the control (20.07 ± 7.55, P = 0.018). Immunohistochemistry confirmed a decrease in cellular proliferation after MBP with 23.4 ± 7.8% of the cells staining positive for Ki-67 in the MBP group versus 28.6 ± 7.9% in the control group (P = 0.006). CONCLUSIONS: MBP has a negative impact on cellular proliferation and intracellular transport of butyrate within the rat colon, not related to apoptosis. This is the first study to demonstrate the intracellular effects that MBP has on the rat colon.

Tuberculosis in Sudan: a study of Mycobacterium tuberculosis strain genotype and susceptibility to anti-tuberculosis drugs.

BACKGROUND: Sudan is a large country with a diverse population and history of civil conflict. Poverty levels are high with a gross national income per capita of less than two thousand dollars. The country has a high burden of tuberculosis (TB) with an estimated 50,000 incident cases during 2009, when the estimated prevalence was 209 cases per 100,000 of the population. Few studies have been undertaken on TB in Sudan and the prevalence of drug resistant disease is not known. METHODS: In this study Mycobacterium tuberculosis isolates from 235 patients attending three treatment centers in Sudan were screened for susceptibility to isoniazid, rifampicin, ethambutol and streptomycin by the proportion method on Lowenstein Jensen media. 232 isolates were also genotyped by spoligotyping. Demographic details of patients were recorded using a structured questionnaire. Statistical analyses were conducted to examine the associations between drug resistance with risk ratios computed for a set of risk factors (gender, age, case status--new or relapse, geographic origin of the patient, spoligotype, number of people per room, marital status and type of housing). RESULTS: Multi drug-resistant tuberculosis (MDR-TB), being resistance to at least rifampicin and isoniazid, was found in 5% (95% CI: 2,8) of new cases and 24% (95% CI: 14,34) of previously treated patients. Drug resistance was associated with previous treatment with risk ratios of 3.51 (95% CI: 2.69-4.60; p < 0.001) for resistance to any drug and 5.23 (95% CI: 2.30-11.90; p < 0.001) for MDR-TB. Resistance was also associated with the geographic region of origin of the patient, being most frequently observed in patients from the Northern region and least in the Eastern region with risk ratios of 7.43 (95%CI:3.42,16.18; p: < 0.001) and 14.09 (95%CI:1.80,110.53; p:0.026) for resistance to any drug and MDR-TB. The major genotype observed was of the Central Asia spoligotype family (CAS1_Delhi), representing 49% of the 232 isolates examined. CONCLUSIONS: We conclude that emergence of drug resistant tuberculosis has the potential to be a serious public health problem in Sudan and that strengthened tuberculosis control and improved monitoring of therapy is needed. Further surveillance is required to fully ascertain the extent of the problem.

2,3-butanediol production by acetogenic bacteria, an alternative route to chemical synthesis, using industrial waste gas.

2,3-Butanediol (23BD) is a high-value chemical usually produced petrochemically but which can also be synthesized by some bacteria. To date, the best microbial 23BD production rates have been observed using pathogenic bacteria in fermentation systems that depend on sugars as the carbon and energy sources for product synthesis. Here we present evidence of 23BD production by three nonpathogenic acetogenic Clostridium species-Clostridium autoethanogenum, C. ljungdahlii, and C. ragsdalei-using carbon monoxide-containing industrial waste gases or syngas as the sole source of carbon and energy. Through an analysis of the C. ljungdahlii genome, the complete pathway from carbon monoxide to 23BD has been proposed. Homologues of the genes involved in this pathway were also confirmed for the other two species investigated. A gene expression study demonstrates a correlation between mRNA accumulation from 23BD biosynthetic genes and the onset of 23BD production, while a broader expression study of Wood-Ljungdahl pathway genes provides a transcription-level view of one of the oldest existing biochemical pathways.

CAML does not modulate tetherin-mediated restriction of HIV-1 particle release.

BACKGROUND: Tetherin/BST-2 is a recently-identified potent restriction factor in human cells that restricts HIV particle release following particle formation and budding at the plasma membrane. Vpu counteracts tetherin's restriction of particle release in a manner that has not yet been fully defined. We recently identified calcium-modulating cyclophilin ligand (CAML) as a Vpu-interacting protein that also restricts particle release. We hypothesized that CAML may act to enhance tetherin-mediated restriction of particle release and thereby explain how two distinct factors could be responsible for Vpu-responsive restriction. METHODOLOGY/PRINCIPAL FINDINGS: Endogenous levels of tetherin in human cells correlated well with their restriction pattern and responsiveness to Vpu, while levels of cellular CAML protein did not. Tetherin but not CAML was inducible by interferon in a wide variety of human cells. Stable depletion of human CAML in restrictive HeLa cells had no effect on cell surface levels of tetherin, and failed to relieve tetherin-mediated restriction. Stable depletion of tetherin from HeLa cells, in contrast, rendered HeLa cells permissive and Vpu-unresponsive. Tetherin but not CAML expression in permissive human cells rendered them restrictive and Vpu responsive. Depletion of CAML had no influence on cell surface levels of tetherin. CONCLUSIONS/SIGNIFICANCE: We conclude that tetherin restricts particle release and does not require CAML for this effect. Furthermore, these results do not support a major role for CAML in restricting HIV particle release in human cells.