Robotic surgery versus conventional laparoscopy in sigmoid colectomy for diverticular disease-a comparison of operative trauma and cost-effectiveness: retrospective, single-center analysis.

PURPOSE: Robotic assisted surgery is an alternative, fast evolving technique for performing colorectal surgery. The primary aim of this single center analysis is to compare elective laparoscopic and robotic sigmoid colectomies for diverticular disease on the extent of operative trauma and the costs. METHODS: Retrospective analysis from our prospective clinical database to identify all consecutive patients aged ≥ 18 years who underwent elective minimally invasive left sided colectomy for diverticular disease from January 2016 until December 2020 at our tertiary referral institution. RESULTS: In total, 83 patients (31 female and 52 male) with sigmoid diverticulitis underwent elective minimally invasive sigmoid colectomy, of which 42 underwent conventional laparoscopic surgery (LS) and 41 robotic assisted surgery (RS). The mean C-reactive protein difference between the preoperative and postoperative value was significantly lower in the robotic assisted group (4,03 mg/dL) than in the laparoscopic group (7.32 mg/dL) (p = 0.030). Similarly, the robotic´s hemoglobin difference was significantly lower (p = 0.039). The first postoperative bowel movement in the LS group occurred after a mean of 2.19 days, later than after a mean of 1.63 days in the RS group (p = 0.011). An overview of overall charge revealed significantly lower total costs per operation and postoperative hospital stay for the robotic approach, 6058 € vs. 6142 € (p = 0,014) not including the acquisition and maintenance costs for both systems. CONCLUSION: Robotic colon resection for diverticular disease is cost-effective and delivers reduced intraoperative trauma with significantly lower postoperative C-reactive protein and hemoglobin drift compared to conventional laparoscopy.

Safety, feasibility, and short-term-outcome of anal endoscopic submucosal dissection for anal intraepithelial neoplasia: an option for focal lesions?

BACKGROUND: Anal intraepithelial neoplasia (AIN) appears in three different stages. AIN 1 and AIN 2 (p16 negative) are defined as low risk and unlikely to progress to invasive anal cancer. AIN 2 (p16 positive) and AIN 3 are of high risk and should be treated because progression rates to anal cancer are around 10% and treatment significantly reduces this risk. The correct treatment is still a matter of debate. Human papilloma virus (HPV) plays a role in the development of AIN. Our aim was to assess anal endoscopic dissection (aESD) as an intervention for AIN3. METHODS: We retrospectively evaluated patients who underwent aESD for AIN 3 between December 2017 and March 2023. The interventional technique itself (duration, complications, size of specimen) and patient outcomes (recurrence, progression to anal cancer, re-intervention) were analyzed. RESULTS: Fifteen patients with a median age of 52 years (23-78) underwent aESD for AIN 3. All tested specimens were positive for HPV. Median duration of intervention was 56.1 min, one delayed postinterventional bleeding occurred, and specimen size was 12.05 cm2. Median follow-up was 11.17 months. Three recurrences (20%) appeared: one was resected via biopsy and two were again treated with aESD. There was no progression to invasive anal cancer in the follow-up period. CONCLUSIONS: Anal endoscopic submucosal dissection seems to be a safe and feasible treatment for AIN. Recurrences are seldom and can be treated again with the same method. Nevertheless, indications for resection in comparison to radiofrequency ablation, pharmacological therapy, and watch-and-wait strategy are still unclear. TRIAL REGISTRATION: Ethics commission of Salzburg, Austria, EK-Nr. 1056/2023. Keywords: Endoscopic submucosal dissection, anal intraepithelial neoplasia, anal cancer.

Short-term results after laparoscopic repair of giant hiatal hernias with pledgeted sutures: a retrospective analysis.

PURPOSE: This study investigates if pledgeted sutures for hiatal closure could be an alternative to mesh for the surgical treatment of large hiatal hernia. METHODS: Forty-one patients who underwent laparoscopic 270° Toupet fundoplication with pledgeted sutured crura between September 2014 and April 2017 were evaluated with regard to recurrence of hiatal hernia at 3 months and 1 year after surgery. Indication for pledgets was a hiatal surface area of at least 5.60 cm2, or migration of more than 1/3 of the stomach into the thorax or preoperative hernia size > 5 cm. The integrity of repair was assessed using a barium swallow test 3 months and 1 year after surgery. RESULTS: All operations could be completed laparoscopically with no intraoperative complications. Until study end no complications related to the pledgets have occurred. Forty-four of 50 patients (88.0%) completed the follow-up radiographic examination 3 months (mean 12.7 weeks) after surgery, and 37 patients (74.0%; mean 55.1 weeks) 1 year after surgery. Postoperative recurrence was diagnosed in 3/44 patients (6.8%) at 3 months, and in 4/37 patients (10.8%) at 1 year follow-up. Only one patient was symptomatic, 1 year after surgery (2.7%). All other patients with reherniations were asymptomatic at time of the study. CONCLUSIONS: Utilization of pledgets to reinforce hiatal sutures seems safe and shows a quite low early recurrence rate compared to other methods. Long-term data will allow firm conclusions as to whether pledgeted sutures are an appropriate solution for the treatment of giant hiatal hernias.

Subjective memory complaints in patients with epilepsy: The role of depression, psychological distress, and attentional functions.

While objective memory dysfunctions have been thoroughly investigated in patients with epilepsy, assessment of subjective memory complaints (SMC) remains challenging. Former studies have demonstrated an impact of patients' depressive mood on SMC. However, the impact of more general psychological distress and cognitive functioning in non-memory domains on SMC has only received little attention so far. We therefore sought to determine the factors which may particularly predict SMC in a sample of patients with focal epilepsy (n=99) who accomplished (1) a comprehensive neuropsychological assessment, (2) a subjective memory questionnaire, and (3) scales of self-rated depressive mood and psychological distress. General psychological distress (as measured by the Symptom Checklist- 90-Revised) accounted for a high proportion of SMC and, critically, explained more variance than depressive mood as a single factor (as measured by the Beck Depression Inventory II). Furthermore, SMC were predicted by recall measures of a verbal serial learning task, but also by measures of attention, importantly. Hence, our data firstly indicate that beyond the impact of depressive mood, SMC may be more accurately explained by psychological distress in a more general sense. Secondly, our study provides evidence that patients' estimation of subjective memory is not solely based on functioning in memory domains. Attentional resources may also be critical for patients' perception of everyday memory functioning.

Diagnosis and features of hospital-acquired pneumonia: a retrospective cohort study.

BACKGROUND: Hospital-acquired pneumonia (HAP) is defined as radiologically confirmed pneumonia occurring ≥48h after hospitalization, in non-intubated patients. Empirical treatment regimens use broad-spectrum antimicrobials. AIM: To evaluate the accuracy of the diagnosis of HAP and to describe the demographic and microbiological features of patients with HAP. METHODS: Medical and surgical inpatients receiving intravenous antimicrobials for a clinical diagnosis of HAP at a UK tertiary care hospital between April 2013 and 2014 were identified. Demographic and clinical details were recorded. FINDINGS: A total of 166 adult patients with a clinical diagnosis of HAP were identified. Broad-spectrum antimicrobials were prescribed, primarily piperacillin-tazobactam (57.2%) and co-amoxiclav (12.5%). Sputum from 24.7% of patients was obtained for culture. Sixty-five percent of patients had radiological evidence of new/progressive infiltrate at the time of HAP treatment, therefore meeting HAP diagnostic criteria (2005 American Thoracic Society/Infectious Diseases Society of America guidelines). Radiologically confirmed HAP was associated with higher levels of inflammatory markers and sputum culture positivity. Previous surgery and/or endotracheal intubation were associated with radiologically confirmed HAP. A bacterial pathogen was identified from 17/35 sputum samples from radiologically confirmed HAP patients. These were Gram-negative bacilli (N = 11) or Staphylococcus aureus (N = 6). Gram-negative bacteria tended to be resistant to co-amoxiclav, but susceptible to ciprofloxacin, piperacillin-tazobactam and meropenem. Five of the six S. aureus isolates were meticillin susceptible and all were susceptible to doxycycline. CONCLUSION: In ward-level hospital practice 'HAP' is an over-used diagnosis that may be inaccurate in 35% of cases when objective radiological criteria are applied. Radiologically confirmed HAP represents a distinct clinical and microbiological phenotype. Potential risk factors were identified that could represent targets for preventive interventions.

First human magnetic resonance visualisation of prosthetics for laparoscopic large hiatal hernia repair.

PURPOSE: Mesh repair of large hiatal hernias has increasingly gained popularity to reduce recurrence rates. Integration of iron particles into the polyvinylidene fluoride mesh-based material allows for magnetic resonance visualisation (MR). METHODS: In a pilot prospective case series eight patients underwent surgical repair of hiatal hernias repair with pre-shaped meshes, which were fixated with fibrin glue. An MR investigation with a qualified protocol was performed on postoperative day four and 3 months postoperatively to evaluate the correct position of the mesh by assessing mesh appearance and demarcation. The total MR-visible mesh surface area of each implant was calculated and compared with the original physical mesh size to evaluate potential reduction of the functional mesh surfaces. RESULTS: We documented no mesh migrations or dislocations but we found a significant decrease of MR-visualised total mesh surface area after release of the pneumoperitoneum compared to the original mesh size (mean 78.9 vs 84 cm(2); mean reduction of mesh area = 5.1 cm(2), p < 0.001). At 3 months postoperatively, a further reduction of the mesh surface area could be observed (mean 78.5 vs 78.9 cm(2); mean reduction of mesh area = 0.4 cm(2), p < 0.037). CONCLUSION: Detailed mesh depiction and accurate assessment of the surrounding anatomy could be successfully achieved in all cases. Fibrin glue seems to provide effective mesh fixation. In addition to a significant early postoperative decrease in effective mesh surface area a further reduction in size occurred within 3 months after implantation.

[Interventional procedures in the treatment of gastroesophageal reflux disease]. / Interventionelle Verfahren in der Therapie der gastroösophagealen Refluxkrankheit.

For patients with gastroesophageal reflux disease (GERD) who suffer from severe symptoms despite adequate medical therapy, interventional procedures are the only option for improving symptoms and thus the quality of life. In the clinical practice it is decisive if a hiatal hernia (HH) is present or not and whether it is larger or smaller than 2-3 cm. Patients who have a HH > 2-3 cm should undergo laparoscopic fundoplication with hiatal hernia repair. Patients with a larger HH are no longer eligible for endoscopic therapy as closure of the HH is not endoscopically possible. With the new laparoscopic methods (e.g. LINX and electrical stimulation) HH closure is theoretically possible but sufficient data is lacking. Furthermore, if a hiatal closure is additionally carried out the actual advantages of these methods are partly lost. Currently, outside of clinical trials only laparoscopic fundoplication can be recommended for patients with GERD and HH, because convincing long-term data are only available for this method. It seems that in clinical practice it is not so important what type of fundoplication is performed, more important seems to be the experience of the surgeon with the technique.

"Acute intrathoracic stomach!" How should we deal with complicated type IV paraesophageal hernias?

PURPOSE: Management of emergently admitted patients due to a complicated large paraesophageal hernia with acute symptoms of an "intrathoracic stomach" is controversial. The aim of this study was to clarify whether emergency surgery in such cases should be the procedure of choice. METHODS: The retrospective analysis of patients who were hospitalized due to emerging acute symptoms of an "intrathoracic stomach" between January 2009 and May 2013 was used as method. Patients were categorized into three groups: emergency operation within 24 h after admission, semi-elective operation within the first 7 days after admission and elective operation. RESULTS: Twenty-four patients were identified. Only three (12.5 %) patients required laparoscopic emergency surgery and two incurred a perioperative complication. In consequence of persistent or early recurrent complaints a laparoscopic operation was required prior to discharge semi-elective in 6/24 (25 %) patients without complications. The remaining 15/24 (62.5 %) patients were free of complaints after conservative therapy, but all of them decided upon elective operation after informed consent. One minor complication occurred. CONCLUSION: The majority of patients with acute symptoms due to an intrathoracic stomach can primarily be treated conservatively and timing of elective repair should be performed after resuscitation in a center of laparoscopic antireflux surgery.

[Component separation for closing large abdominal wall defects: evolution of a method from 1990 to present day]. / Die Komponentenseparation zum Verschluss komplexer Bauchwandhernien: Entwicklung einer Technik von 1990 bis heute.

BACKGROUND: The separation of autologous and functional active components of the lateral abdominal wall for closing large midline defects was introduced in 1990. The original components separation technique (CS) has undergone numerous modifications. The aim of this work is to summarise the essential steps of the development. METHODS: Based on a literature review, the original technique, the modifications and advancements are presented and evaluated regarding indication, techniques and results. RESULTS: The original technique still has a high status, because of the large extent of rectus complex medialisation. Numerous modifications of the anterior conventional component separation with different clinical results were described. The development of a minimally invasive technique with balloon dilatation trocars was an essential step and decreased wound morbidity. The modified posterior component separation by transverse abdominis release currently seems to be an encouraging alternative to be regarded as a widening of the sublay technique. All methods can be combined with implantation of prosthetic or biological implants in intraperitoneal, sublay or onlay technique, whereby the recurrence rate can be decreased. CONCLUSION: From where we stand today no single technique can generally be recommended. The latest methods aim for decreasing complications and recurrences by means of minimally invasive procedures. The surgical strategy still depends on the complexity and extent of abdominal wall defect and has to be determined according to individual aspects and sometimes requires an interdisciplinary approach.

Parastomal hernia repair with a 3-D mesh device and additional flat mesh repair of the abdominal wall.

PURPOSE: Parastomal hernias (PSHs) have been a major clinical problem. The aim of this study was to evaluate a new method of PSH repair in combination with an additional flat mesh reinforcement of the abdominal wall. METHODS: In a pilot case series, seven patients suffering from complex PSHs (≥5 cm diameter and/or recurrence) underwent surgery and were treated by intraperitoneal onlay technique (IPOM) with a synthetic 3-D funnel-shaped mesh implant. The demographics, perioperative, and follow-up data are presented in this report. RESULTS: The surgical strategy varied between purely laparoscopic (n = 1), laparoscopically assisted (hybrid n = 3), or open techniques (n = 3) using original or suture-reconstructed mesh devices. The funnel mesh implantations in IPOM technique were combined with attached flat meshes in the appropriate position of the abdominal wall. No procedure-related complications occurred. The mean length of hospital stay was 12 days and the mean operating time was 171 min. No recurrence of PSH or incisional hernias was observed during a mean follow-up period of 12.3 months (range from 7 to 22). CONCLUSION: The use of a 3-D mesh implant has so far shown to be a promising option in the treatment of primary and recurrent PSHs. Its use proved to be reasonable in both laparoscopic and open IPOM technique. PSHs were preferably repaired using the original, unmodified implant, but when we also found it safe to incise, place and then suture the mesh around the pre-existing ostomy.

Routine versus no drain placement after elective laparoscopic cholecystectomy: meta-analysis of randomized controlled trials.

Routine drainage of the subhepatic space has been a surgical trend of open cholecystectomy, carried on to the era of laparoscopic surgery without substantial evidence. Avoiding the potentially devastating sequelae of an undetected bile leakage is the main rationale behind this practice. Aim of this meta-analysis was to compare evidence on routine drain placement after laparoscopic cholecystectomy versus no drainage. A meta-analysis of randomized controlled trials was conducted; outcome variables included postoperative pain, subhepatic collection, 30-day morbidity, wound-related complications, and drainage interventions. The fixed- and random effects models were used in order to calculate combined overall effect sizes of pooled data. Data are presented as the odds ratio (OR) or difference in means with 95% confidence interval (CI). Six randomized trials including 1167 patients were identified. Pain scores were significantly higher in the drainage group both at 6-12h (mean difference 1.12, 95% CI 1.01-1.24, P<0.0001) and at 12-24h after surgery (mean difference 1.12, 95% CI 0.86-1.39, P<0.0001). No difference was found with regard to the incidence of subhepatic collection and drainage procedures. A trend in favor of the no drain approach with regard to 30-day morbidity and wound infection was registered, although this was less pronounced after sensitivity analysis. The possible clinical benefit of routine use of abdominal drainage in uncomplicated laparoscopic cholecystectomies requires larger study populations. The approach is however not encouraged on the basis of the present analysis, as it results in increased postoperative pain and overall morbidity.

[Diagnosis and surgical therapy of hiatal hernia]. / Diagnose und chirurgische Therapie der Hiatushernie.

Using the usual diagnostic tools like barium swallow examination, endoscopy, and manometry, we are able to diagnose a hiatal hernia, but it is not possible to predict the size of the hernia opening or, respectively, the size of the hiatal defect. At least a correlation can be expected if the gastroesophageal junction is endoscopically assessed in a retroflexed position, and graded according to Hill. So far, it is not possible to come to a clear conclusion how the hiatal closure during hiatal hernia repair should be performed. There is no consensus on using a mesh, and when using a mesh which type or shape should be used. Further studies including long-term results on this issue are necessary. However, it seems obvious to make the decision depending on certain conditions found during operation, and not on preoperative findings.

Predictability of hiatal hernia/defect size: is there a correlation between pre- and intraoperative findings?

PURPOSE: Closure of the esophageal hiatus is an important step during laparoscopic antireflux surgery and hiatal hernia surgery. The aim of this study was to investigate the correlation between the preoperatively determined hiatal hernia size and the intraoperative size of the esophageal hiatus. METHODS: One hundred patients with documented chronic gastroesophageal reflux disease underwent laparoscopic fundoplication. All patients had been subjected to barium studies before surgery, specifically to measure the presence and size of hiatal hernia. The size of the esophageal hiatus was measured during surgery by calculating the hiatal surface area (HSA). HSA size >5 cm(2) was defined as large hiatal defect. Patients were grouped according to radiologic criteria: no visible hernia (n = 42), hernia size between 2 and 5 cm (n = 52), and >5 cm (n = 6). A retrospective correlation analysis between hiatal hernia size and intraoperative HSA size was undertaken. RESULTS: The mean radiologically predicted size of hiatal hernias was 1.81 cm (range 0-6.20 cm), while the interoperative measurement was 3.86 cm(2) (range 1.51-12.38 cm(2)). No correlation (p < 0.05) was found between HSA and hiatal hernia size for all patients, and in the single radiologic groups, 11.9 % (5/42) of the patients who had no hernia on preoperative X-ray study had a large hiatal defect, and 66.6 % (4/6) patients with giant hiatal hernia had a HSA size <5 cm(2). CONCLUSIONS: The study clearly demonstrates that a surgeon cannot rely on preoperative findings from the barium swallow examination, because the sensitivity of a preoperative swallow is very poor.

Similar symptom patterns in gastroesophageal reflux patients with and without hiatal hernia.

Gastroesophageal reflux disease is a common clinical entity in Western societies. Its association with hiatal hernia has been well documented; however, the comparative clinical profile of patients in the presence or absence of hiatal hernia remains mostly unknown. The aim of the present study was to delineate and compare symptom, impedance, and manometric patterns of patients with and without hiatal hernia. A cumulative number of 120 patients with reflux disease were enrolled in the study. Quality of life score, demographic, symptom, manometric, and impedance data were prospectively collected. Data comparison was undertaken between patients with and without hiatal hernia. A P-value < 0.05 was considered statistically significant. Patients with hiatal hernia tended to be older than patients without hernia (52.3 vs. 48.6 years, P < 0.05), whereas quality of life scores were slightly better for the former (97.0 vs. 88.2, P= 0.005). Regurgitation occurred more frequently in patients without hiatal hernia (78.3% vs. 93.9%, P < 0.05). Otherwise, no differences were found with regard to esophageal and extraesophageal symptoms. However, lower esophageal sphincter pressures (7.7 vs. 10.0 mmHg, P= 0.007) and more frequent reflux episodes (upright, 170 vs. 134, P= 0.01; supine, 41 vs. 24, P < 0.03) were documented for patients with hiatal hernia on manometric and impedance studies. Distinct functional characteristics in patients with and without hiatal hernia may suggest a tailored therapeutic management for these diverse patient groups.

Comparing long-term toxicity and efficacy of combined modality treatment including extended- or involved-field radiotherapy in early-stage Hodgkin's lymphoma.

BACKGROUND: To evaluate long-term toxicity and efficacy of a combined modality strategy including extended-field radiotherapy (EF-RT) or involved-field radiotherapy (IF-RT), the German Hodgkin Study Group carried out a follow-up analysis in patients with early unfavorable Hodgkin's lymphoma (HL). PATIENTS AND METHODS: One thousand two hundred and four patients were randomized to four cycles of chemotherapy followed by either 30 Gy EF- or 30 Gy IF-RT (HD8 trial); 532 patients in each treatment arm were eligible. RESULTS: At 10 years, no arm differences were revealed with respect to freedom from treatment failure (FFTF) (79.8% versus 79.7%), progression-free survival (79.8% versus 80.0%), and overall survival (86.4% versus 87.3%). Non-inferiority of IF-RT was demonstrated for the primary end point FFTF (95% confidence interval for hazard ratio 0.72-1.25). Elderly patients had a poorer outcome when treated with EF-RT. So far, 15.0% of patients in arm A and 12.2% in arm B died, mostly due to secondary malignancies (5.3% versus 3.4%) or HL (3.2% versus 3.4%). After EF-RT, there were more secondary malignancies overall (58 versus 45), especially acute myeloid leukemias (11 versus 4). CONCLUSION: Radiotherapy intensity reduction to IF-RT does not result in poorer long-term outcome but is associated with less acute toxicity and might be associated with less secondary malignancies.

Influence of the esophageal hiatus size on the lower esophageal sphincter, on reflux activity and on symptomatology.

Hiatal hernia is an underlying factor contributing to gastroesophageal reflux disease (GERD). However, it remains elusive whether the size of the esophageal hiatus has a de facto influence on the lower esophageal sphincter (LES), on the intensity of patient reflux, on GERD symptoms and on the quality of life (QoL). One hundred patients with documented chronic GERD underwent laparoscopic fundoplication. QoL was evaluated before surgery using the Gastrointestinal Quality of Life Index (GIQLI). Additionally, GERD symptoms and nonspecific gastrointestinal symptoms were documented using a standardized questionnaire (score 0-224). The size of the esophageal hiatus was measured during surgery by calculating the hiatal surface area (HSA). Correlation analysis between the preoperative QoL, GERD symptoms, esophageal manometry, multichannel intraluminal impedance monitoring data and HSA size was performed, in order to investigate whether the HSA has an influence on the patients'symptoms, GIQLI, manometry and multichannel intraluminal impedance monitoring data. Statistical significance was set at a P-value of 0.05. The HSA sizes ranged from 1.51cm(2) to 16.09cm(2) (mean 4.14cm(2) ). The preoperative GIQLI ranged from 15 points to 133 points (mean 94.37 points). Symptom scores ranged from 2 points to 192 points (mean 49.84 points). No significant influence of the HSA on GIQLI or preoperative symptoms was recorded. HSA size had a significant negative effect on LES pressure. Additionally, there was a significant positive correlation between HSA size and number of refluxes in supine position. For the rest of the evaluated data, including DeMeester score, total number of refluxes, refluxes in upright position, acid reflux events, proximal reflux events, LES length and body motility, no significant correlation was found. Although patients subjectively are not significantly affected by the size of the hiatus, it has significant effects on the LES pressure and on gastroesopageal reflux in supine position.

An investigation of transmission ratio distortion in the central region of the human MHC.

Transmission ratio distortion (TRD) describes a significant departure from expected Mendelian inheritance ratios that is fundamental to both the biology of reproduction and statistical genetics. The relatively high fetal wastage in humans, with consequent selection of alleles in utero, makes it likely that TRD is prevalent in the human genome. The central region of the human major histocompatibility complex (MHC) is a strong TRD candidate, as it houses a number of immune and regulatory genes that may be important in pregnancy outcome. We used a nonhaplotype-based method to select 13 tagging SNPs from three central MHC candidate regions, and analysed their transmission in 380 newborns and their parents (1138 individuals). A TRD of 54:46 was noted in favour of the common allele of a promoter SNP in the CLIC1 gene (P = 0.025), with a similar distortion using haplotypes across the same gene region (P = 0.016). We also found evidence that markers in the CLIC1 gene region may have been subject to recent selection (P < 0.001). The study illustrates the potential benefits of screening for TRD and highlights the difficulties encountered therein.

Cooperative effects in hydrogen-bonding of protein secondary structure elements: a systematic analysis of crystal data using Secbase.

A systematic analysis of the hydrogen-bonding geometry in helices and beta sheets has been performed. The distances and angles between the backbone carbonyl O and amide N atoms were correlated considering more than 1500 protein chains in crystal structures determined to a resolution better than 1.5 A. They reveal statistically significant trends in the H-bond geometry across the different secondary structural elements. The analysis has been performed using Secbase, a modular extension of Relibase (Receptor Ligand Database) which integrates information about secondary structural elements assigned to individual protein structures with the various search facilities implemented into Relibase. A comparison of the mean hydrogen-bond distances in alpha helices and 3(10) helices of increasing length shows opposing trends. Whereas in alpha helices the mean H-bond distance shrinks with increasing helix length and turn number, the corresponding mean dimension in 3(10) helices expands in a comparable series. Comparing similarly the hydrogen-bond lengths in beta sheets there is no difference to be found between the mean H-bond length in antiparallel and parallel beta sheets along the strand direction. In contrast, an interesting systematic trend appears to be given for the hydrogen bonds perpendicular to the strands bridging across an extended sheet. With increasing number of accumulated strands, which results in a growing number of back-to-back piling hydrogen bonds across the strands, a slight decrease of the mean H-bond distance is apparent in parallel beta sheets whereas such trends are obviously not given in antiparallel beta sheets. This observation suggests that cooperative effects mutually polarizing spatially well-aligned hydrogen bonds are present either in alpha helices and parallel beta sheets whereas such influences seem to be lacking in 3(10) helices and antiparallel beta sheets.

Investigation of malaria susceptibility determinants in the IFNG/IL26/IL22 genomic region.

Interferon-gamma, encoded by IFNG, is a key immunological mediator that is believed to play both a protective and a pathological role in malaria. Here, we investigate the relationship between IFNG variation and susceptibility to malaria. We began by analysing West African and European haplotype structure and patterns of linkage disequilibrium across a 100 kb genomic region encompassing IFNG and its immediate neighbours IL22 and IL26. A large case-control study of severe malaria in a West Africa population identified several weak associations with individual single-nucleotide polymorphisms in the IFNG and IL22 genes, and defined two IL22 haplotypes that are, respectively, associated with resistance and susceptibility. These data provide a starting point for functional and genetic analysis of the IFNG genomic region in malaria and other infectious and inflammatory conditions affecting African populations.