Identification of MHC class II restricted T-cell-mediated reactivity against MHC class I binding Mycobacterium tuberculosis peptides

Major histocompatibility complex (MHC) class I restricted cytotoxic T lymphocytes (CTL) are known to play an important role in the control of Mycobacterium tuberculosis infection so identification of CTL epitopes from M. tuberculosis is of importance for the development of effective peptide-based vaccines. In the present work, bioinformatics technology was employed to predict binding motifs of 9mer peptides derived from M. tuberculosis for the 12 HLA-I supertypes. Subsequently, the predicted peptides were synthesized and assayed for binding to HLA-I molecules in a biochemically based system. The antigenicity of a total of 157 peptides with measured affinity for HLA-I molecules of K(D) ≤ 500 nM were evaluated using peripheral blood T cells from strongly purified protein derivative reactive healthy donors. Of the 157 peptides, eight peptides (5%) were found to induce T-cell responses. As judged from blocking with HLA class I and II subtype antibodies in the ELISPOT assay culture, none of the eight antigenic peptides induced HLA class I restricted CD8(+) T-cell responses. Instead all responses were blocked by pan-HLA class II and anti-HLA-DR antibodies. In addition, CD4(+) T-cell depletion before the 10 days of expansion, resulted in total loss of reactivity in the ELISPOT culture for most peptide specificities. FACS analyses with intracellular interferon-γ staining of T cells expanded in the presence of M. tuberculosis peptides confirmed that the responsive cells were indeed CD4(+). In conclusion, T-cell immunity against HLA-I binding 9mer M. tuberculosis-derived peptides might in many cases turn out to be mediated by CD4(+) T cells and restricted by HLA-II molecules. The use of 9mer peptides recognized by both CD8(+) and CD4(+) T cells might be of importance for the development of future M. tuberculosis peptide-based vaccines.     

Efficacy of cognitive behavioral internet-based therapy in parents after the loss of a child during pregnancy: pilot data from a randomized controlled trial

The loss of a child during pregnancy can be a traumatic event associated with long-lasting grief and psychological distress. This study examined the efficacy of an internet-based cognitive behavioral therapy program for mothers after pregnancy loss. In a randomized controlled trial with a waiting list control group, 83 participants who had lost a child during pregnancy were randomly allocated either to 5 weeks of internet therapy or to a 5-week waiting condition. Within a manualized cognitive behavioral treatment program, participants wrote ten essays on loss-specific topics. Posttraumatic stress, grief, and general psychopathology, especially depression, were assessed pretreatment, posttreatment, and at 3-month follow-up. Intention-to-treat analyses and completer analyses were performed. Relative to controls, participants in the treatment group showed significant improvements in posttraumatic stress, grief, depression, and overall mental health, but not in anxiety or somatization. Medium to large effect sizes were observed, and the improvement was maintained at 3-month follow-up. This internet-based cognitive behavioral therapy program represents an effective treatment approach with stable effects for women after pregnancy loss. Implementation of the program can thus help to improve the health care provision for mothers in this traumatic loss situation.     

Significance and clinical impact of routinely tested urinary ethyl glucuronide after liver transplantation – development of a risk score

Alcohol abuse after liver transplantation can seriously impact graft and patient survival. However, to date, there is no defined standard procedure to identify patients consuming alcohol after liver transplantation. The aim of this study was to analyze the diagnostic value and clinical impact of routinely measured urinary ethyl glucuronide (uEtG) – a metabolite of ethanol – in patients after liver transplantation. Data of 362 consecutive patients after liver transplantation who visited the University Hospital of Tuebingen for outpatient follow-up were analyzed. Forty-eight patients (13%) displayed positive uEtG results. The uEtG positive group contained significantly more patients with pretransplant alcoholic liver disease. However, two thirds of the uEtG positive patients had no history of pretransplant alcoholic liver disease. Several clinical parameters were significantly associated with positive uEtG. In order to enable a more cost-effective application of uEtG in the future, a clinical risk score was developed (specificity 0.95). In conclusion, routine testing for uEtG reveals a considerable percentage of patients practicing alcohol intake after liver transplantation. Application of our proposed risk score could help focusing uEtG testing on patients at risk.     

Laparoscopic-assisted resection of Meckel's diverticulum in children.

BACKGROUND AND OBJECTIVES: Meckel's diverticulum (MD) presents unique challenges for a pediatric surgeon, as it is prone to varied complications. This case series highlights the diverse presentations and laparoscopic management of MD in children. METHODS: We performed a retrospective analysis of consecutive cases of laparoscopic-assisted transumbilical Meckel's diverticulectomy (LATUM) performed by the same surgeon for incidental as well as diverse Meckel's diverticular complications over 20 months. RESULTS: Eight patients (5 males and 3 females) aged 3 years to 13 years (median, 12) underwent LATUM. Three patients had painless per-rectal bleeding and 1 presented with intestinal obstruction due to a mesodiverticular band and intestinal ischemia. Two patients had features masquerading as appendicitis; one had perforated MD with secondary inflammation of the appendix, and the other had a torsed, gangrenous MD. In 2 patients, incidental MD with a narrow base was noted at appendicectomy for appendicitis. All patients underwent successful LATUM along with appendicectomy in 4 patients. The operative duration was 72 minutes to 165 minutes (mean, 112.1+/-30.6). There were no operative complications, and no conversion to open surgery was required. The hospital stay was 4 days to 7 days (mean, 4.7+/-1.2). The patient with mesodiverticular band intestinal obstruction presented with adhesive intestinal obstruction 2 weeks after the surgery. Laparoscopic-assisted minilaparotomy was done to release the pelvic adhesions. There were no other complications during the follow-up (median, 11 months). CONCLUSIONS: LATUM is a simple, safe, and effective procedure with a better cosmetic outcome that can be performed for diverse manifestations of MD. The technique also allows palpation of the MD and avoids use of expensive staplers.     

The Non‐Motor Symptoms Scale in Parkinson’s disease: Validation and use

The Non‐Motor Symptoms Scale (NMSS) was developed and validated in 2007 as the first instrument for the comprehensive assessment of a range of non‐motor symptoms in Parkinson's disease (PD). Thirteen years have elapsed since its introduction and extensive international validation with good psychometric attributes has been carried out. Here, we review the validation data of the NMSS and its cross‐validity with other scales, and describe the key evidence derived from use of the NMSS in clinical studies. To date, over 100 clinical studies and trials have made use of it as an outcome measure, showing consistent and strong correlations between NMSS burden and health‐related quality of life measures. Moreover, the scale has shown to be capable of detecting longitudinal changes in non‐motor symptoms, where studies have shown differential changes over time of several of the NMSS domains. The scale has become a key outcome in several randomized clinical trials. Highlighting the prevalence and importance of non‐motor symptoms to quality of life in patients with PD, the development of NMSS has also been useful in signposting clinical and biomarker based research addressing non‐motor symptoms in PD.     

A report of 6 children with small bowel intussusception that required surgical intervention

Background/Purpose

We aim to justify the need for surgical intervention in our patients with childhood small bowel intussusceptions (SBIs) and review the current concepts in childhood SBI.

Materials and Methods

We retrospectively reviewed the clinical charts of all patients with surgically confirmed SBI between July 1999 and October 2002. Demographic data, clinical presentation and investigations, operative and pathologic findings, and outcome were analyzed.

Results

Of 173 patients with intussusception, 6 (3.5%) were diagnosed with SBI. Median age was 11 months. Ultrasonography revealed intussusceptions in all patients, but only 1 was diagnosed with SBI. Air enema reductions were attempted in 4 of 6 patients with all ending up in failure and surgery. Surgery revealed ileoileal intussusceptions in 4 patients and jejunojejunal intussusceptions in 2 patients. Two patients had long intussusceptions measuring between 30 and 50 cm in length. Five patients had pathologic lead points, and bowel complications occurred in 2 patients. All underwent bowel resection and primary anastomosis.

Conclusion

Despite reports on spontaneous reduction of SBI, surgery was unavoidable in all our patients with SBI because of the presence of pathologic lead points and/or bowel complications. Air enema reduction was ineffective in SBI. Due caution should be exercised when selecting patients for expectant management.     

Perceptual analysis of speech and the activity in the lateral pharyngeal walls before and after velopharyngeal flap surgery

The purpose of this study was to investigate the effects of velopharyngeal flap surgery on speech and its relation with the activity in the lateral pharyngeal wall. Videofluoroscopic recordings made before and after operation were used in this retrospective study, which comprised 28 patients who had pharyngeal flap surgery between 5:5 and 14:3 (mean 8:6) years:months of age at the Sahlgrenska University Hospital, Göteborg, Sweden. Twenty-four patients had different types of clefts and four had velopharyngeal impairment (VPI) without a cleft palate. Eleven had additional malformations. Speech and activity in the lateral pharyngeal walls were rated perceptually preoperatively and postoperatively. The study confirmed that patients with VPI can be helped by a velopharyngeal flap operation. There seemed to be a relation with the activity in the lateral pharyngeal wall and speech. The later the postoperative assessment, the better the speech, but the age at operation did not affect the result. The impact of additional anomalies and syndromes should be investigated further.     

Potential routes for indirect transmission of African swine fever virus into domestic pig herds

Following its introduction into Georgia in 2007, African swine fever virus (ASFV) has become widespread on the European continent and in Asia. In many cases, the exact route of introduction into domestic pig herds cannot be determined, but most introductions are attributed to indirect virus transmission. In this review, we describe knowledge gained about different matrices that may allow introduction of the virus into pig herds. These matrices include uncooked pig meat, processed pig‐derived products, feed, matrices contaminated with the virus and blood‐feeding invertebrates. Knowledge gaps still exist, and both field studies and laboratory research are needed to enhance understanding of the risks for ASFV introductions, especially via virus‐contaminated materials, including bedding and feed, and via blood‐feeding, flying insects. Knowledge obtained from such studies can be applied to epidemiological risk assessments for the different transmission routes. Such assessments can be utilized to help predict the most effective biosecurity and control strategies.