Long-term outcomes after close rectal dissection and total mesorectal excision in ileal pouch-anal anastomosis for ulcerative colitis.

BACKGROUND: During ileal pouch-anal anastomosis (IPAA) surgery for ulcerative colitis (UC), rectal dissection can be performed via close rectal dissection (CRD) or in a total mesorectal excision plane (TME). Although CRD should protect autonomic nerve function, this technique may be more challenging than TME. The aim of this study was to compare long-term outcomes of patients undergoing CRD and TME. METHODS: This single-centre retrospective cohort study included consecutive patients who underwent IPAA surgery for UC between January 2002 and October 2017. Primary outcomes were chronic pouch failure (PF) among patients who underwent CRD and TME and the association between CRD and developing chronic PF. Chronic PF was defined as a pouch-related complication occurring ≥ 3 months after primary IPAA surgery requiring redo pouch surgery, pouch excision or permanent defunctioning ileostomy. Secondary outcomes were risk factors and causes for chronic PF. Pouch function and quality of life were assessed via the Pouch dysfunction score and Cleveland global quality of life score. RESULTS: Out of 289 patients (155 males, median age 37 years [interquartile range 26.5-45.5 years]), 128 underwent CRD. There was a shorter median postoperative follow-up for CRD patients than for TME patients (3.7 vs 10.9 years, p < 0.01). Chronic PF occurred in 6 (4.7%) CRD patients and 20 (12.4%) TME patients. The failure-free pouch survival rate 3 years after IPAA surgery was comparable among CRD and TME patients (96.1% vs. 93.5%, p = 0.5). CRD was a no predictor for developing chronic PF on univariate analyses (HR 0.7 CI-95 0.3-2.0, p = 0.54). A lower proportion of CRD patients developed chronic PF due to a septic cause (1% vs 6%, p = 0.03). CONCLUSIONS: Although differences in chronic PF among CRD and TME patients were not observed, a trend toward TME patients developing chronic pelvic sepsis was detected. Surgeons may consider performing CRD during IPAA surgery for UC.

Aberrant patterns of PET response during treatment for DLBCL patients with MYC gene rearrangements.

PURPOSE: MYC gene rearrangements in diffuse large B-cell lymphoma (DLBCL) patients are associated with poor prognosis. Our aim was to compare patterns of 2[18F]fluoro-2-deoxy-D-glucose positron emission tomography computed tomography (PET/CT) response in MYC + and MYC- DLBCL patients. METHODS: Interim PET/CT (I-PET) and end of treatment PET/CT (EoT-PET) scans of 81 MYC + and 129 MYC- DLBCL patients from 2 HOVON trials were reviewed using the Deauville 5-point scale (DS). DS1-3 was regarded as negative and DS4-5 as positive. Standardized uptake values (SUV) and metabolic tumor volume (MTV) were quantified at baseline, I-PET, and EoT-PET. Negative (NPV) and positive predictive values (PPV) were calculated using 2-year overall survival. RESULTS: MYC + DLBCL patients had significantly more positive EoT-PET scans than MYC- patients (32.5 vs 15.7%, p = 0.004). I-PET positivity rates were comparable (28.8 vs 23.8%). In MYC + patients 23.2% of the I-PET negative patients converted to positive at EoT-PET, vs only 2% for the MYC- patients (p = 0.002). Nine (34.6%) MYC + DLBCL showed initially uninvolved localizations at EoT-PET, compared to one (5.3%) MYC- patient. A total of 80.8% of EoT-PET positive MYC + patients showed both increased lesional SUV and MTV compared to I-PET. In MYC- patients, 31.6% showed increased SUV and 42.1% showed increased MTV. NPV of I-PET and EoT-PET was high for both MYC subgroups (81.8-94.1%). PPV was highest at EoT-PET for MYC + patients (61.5%). CONCLUSION: MYC + DLBCL patients demonstrate aberrant PET response patterns compared to MYC- patients with more frequent progression during treatment after I-PET negative assessment and new lesions at sites that were not initially involved. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION: HOVON-84: EudraCT: 2006-005,174-42, retrospectively registered 01-08-2008. HOVON-130: EudraCT: 2014-002,654-39, registered 26-01-2015.

Cryptic introgressions contribute to transgressive segregation for early blight resistance in tomato.

KEY MESSAGE: We identified cryptic early blight resistance introgressions in tomato breeding lines and demonstrated efficient genotypic selection for resistance in the context of a tomato breeding program. Early blight is a widespread and problematic disease affecting tomatoes (Solanum lycopersicum). Caused by the fungal pathogen Alternaria linariae (syn. A. tomatophila), symptoms include lesions on tomato stems, fruit, and foliage, often resulting in yield losses. Breeding tomatoes with genetic resistance would enhance production sustainability. Using cross-market breeding populations, we identified several quantitative trait loci (QTL) associated with early blight resistance. Early blight resistance putatively derived from 'Campbell 1943' was confirmed in modern fresh market tomato breeding lines. This resistance offered substantial protection against early blight stem lesions (collar rot) and moderate protection from defoliation. A distinctive and potentially novel form of early blight foliar resistance was discovered in a processing tomato breeding line and is probably derived from S. pimpinellifolium via 'Hawaii 7998'. Additional field trials validated the three most promising large-effect QTL, EB-1.2, EB-5, and EB-9. Resistance effects for EB-5 and EB-9 were consistent across breeding populations and environments, while EB-1.2's effect was population specific. Using genome-wide marker-assisted backcrossing, we developed fresh market tomato lines that were near-isogenic for early blight QTL. Resistance in these lines was largely mediated by just two QTL, EB-5 and EB-9, that together captured 49.0 and 68.7% of the defoliation and stem lesion variance, respectively. Our work showcases the value of mining cryptic introgressions in tomato lines, and across market classes, for use as additional sources of disease resistance.

CRISPR/CAS9 mutagenesis of a single r-opsin gene blocks phototaxis in a marine larva.

Many marine animals depend upon a larval phase of their life cycle to locate suitable habitat, and larvae use light detection to influence swimming behaviour and dispersal. Light detection is mediated by the opsin genes, which encode light-sensitive transmembrane proteins. Previous studies suggest that r-opsins in the eyes mediate locomotory behaviour in marine protostomes, but few have provided direct evidence through gene mutagenesis. Larvae of the marine annelid Capitella teleta have simple eyespots and are positively phototactic, although the molecular components that mediate this behaviour are unknown. Here, we characterize the spatio-temporal expression of the rhabdomeric opsin genes in C. teleta and show that a single rhabdomeric opsin gene, Ct-r-opsin1, is expressed in the larval photoreceptor cells. To investigate its function, Ct-r-opsin1 was disrupted using CRISPR/CAS9 mutagenesis. Polymerase chain reaction amplification and DNA sequencing demonstrated efficient editing of the Ct-r-opsin1 locus. In addition, the pattern of Ct-r-opsin1 expression in photoreceptor cells was altered. Notably, there was a significant decrease in larval phototaxis, although the eyespot photoreceptor cell and associated pigment cell formed normally and persisted in Ct-r-opsin1-mutant animals. The loss of phototaxis owing to mutations in Ct-r-opsin1 is similar to that observed when the entire photoreceptor and pigment cell are deleted, demonstrating that a single r-opsin gene is sufficient to mediate phototaxis in C. teleta. These results establish the feasibility of gene editing in animals like C. teleta, and extend previous work on the development, evolution and function of the C. teleta visual system . Our study represents one example of disruption of animal behaviour by gene editing through CRISPR/CAS9 mutagenesis, and has broad implications for performing genome editing studies in a wide variety of other understudied animals.

The glutathione transferase Mu null genotype leads to lower 6-MMPR levels in patients treated with azathioprine but not with mercaptopurine.

The conversion of azathioprine (AZA) to mercaptopurine (MP) is mediated by glutathione transferase Mu1 (GSTM1), alpha1 (GSTA1) and alpha2 (GSTA2). We designed a case-control study with data from the TOPIC trial to explore the effects of genetic variation on steady state 6-methylmercaptopurine ribonucleotide (6-MMPR) and 6-thioguanine nucleotide (6-TGN) metabolite levels. We included 199 patients with inflammatory bowel disease (126 on AZA and 73 on MP). GSTM1-null genotype carriers on AZA had two-fold lower 6-MMPR levels than AZA users carrying one or two copies of GSTM1 (2239 (1006-4587) versus 4371 (1897-7369) pmol/8 × 108 RBCs; P<0.01). In patients on MP (control group) 6-MMPR levels were comparable (6195 (1551-10712) versus 6544 (1717-11600) pmol/8 × 108 RBCs; P=0.84). The 6-TGN levels were not affected by the GSTM1 genotype. The presence of genetic variants in GSTA1 and GSTA2 was not related to the 6-MMPR and 6-TGN levels.

Treatment of sporadic Burkitt lymphoma in adults, a retrospective comparison of four treatment regimens.

Burkitt lymphoma is an aggressive B cell malignancy accounting for 1-2% of all adult lymphomas. Treatment with dose-intensive, multi-agent chemotherapy is effective but associated with considerable toxicity. In this observational study, we compared real-world efficacy, toxicity, and costs of four frequently employed treatment strategies for Burkitt lymphoma: the Lymphome Malins B (LMB), the Berlin-Frankfurt-Münster (BFM), the HOVON, and the CODOX-M/IVAC regimens. We collected data from 147 adult patients treated in eight referral centers. Following central pathology assessment, 105 of these cases were accepted as Burkitt lymphoma, resulting in the following treatment groups: LMB 36 patients, BFM 19 patients, HOVON 29 patients, and CODOX-M/IVAC 21 patients (median age 39 years, range 14-74; mean duration of follow-up 47 months). There was no significant difference between age, sex ratio, disease stage, or percentage HIV-positive patients between the treatment groups. Five-year progression-free survival (69%, p = 0.966) and 5-year overall survival (69%, p = 0.981) were comparable for all treatment groups. Treatment-related toxicity was also comparable with only hepatotoxicity seen more frequently in the CODOX/M-IVAC group (p = 0.004). Costs were determined by the number of rituximab gifts and the number of inpatients days. Overall, CODOX-M/IVAC had the most beneficial profile with regards to costs, treatment duration, and percentage of patients completing planned treatment. We conclude that the four treatment protocols for Burkitt lymphoma yield nearly identical results with regards to efficacy and safety but differ in treatment duration and costs. These differences may help guide future choice of treatment.

Quantum Enhancement of the Index of Refraction in a Bose-Einstein Condensate.

We study the index of refraction of an ultracold bosonic gas in the dilute regime. Using phase-contrast imaging with light detuned from resonance by several tens of linewidths, we image a single cloud of ultracold atoms for 100 consecutive shots, which enables the study of the scattering rate as a function of temperature and density using only a single cloud. We observe that the scattering rate is increased below the critical temperature for Bose-Einstein condensation by a factor of 3 compared to the single-atom scattering rate. We show that current atom-light interaction models to second order of the density show a similar increase, where the magnitude of the effect depends on the model that is used to calculate the pair-correlation function. This confirms that the effect of quantum statistics on the index of refraction is dominant in this regime.

Keloids in Rubinstein-Taybi syndrome: a clinical study.

BACKGROUND: Rubinstein-Taybi syndrome (RSTS) is a multiple congenital anomalies-intellectual disability syndrome. One of the complications is keloid formation. Keloids are proliferative fibrous growths resulting from excessive tissue response to skin trauma. OBJECTIVES: To describe the clinical characteristics of keloids in individuals with RSTS reported in the literature and in a cohort of personally evaluated individuals with RSTS. PATIENTS AND METHODS: We performed a literature search for descriptions of RSTS individuals with keloids. All known individuals with RSTS in the Netherlands filled out three dedicated questionnaires. All individuals with (possible) keloids were personally evaluated. A further series of individuals with RSTS from the U.K. was personally evaluated. RESULTS: Reliable data were available for 62 of the 83 Dutch individuals with RSTS and showed 15 individuals with RSTS (24%) to have keloids. The 15 Dutch and 12 U.K. individuals with RSTS with keloids demonstrated that most patients have multiple keloids (n > 1: 82%; n > 5: 30%). Mean age of onset is 11·9 years. The majority of keloids are located on the shoulders and chest. The mean length × width of the largest keloid was 7·1 × 2·8 cm, and the mean thickness was 0·7 cm. All affected individuals complained of itching. Generally, treatment results were disappointing. CONCLUSIONS: Keloids occur in 24% of individuals with RSTS, either spontaneously or after a minor trauma, usually starting in early puberty. Management schedules have disappointing results. RSTS is a Mendelian disorder with a known molecular basis, and offers excellent opportunities to study the pathogenesis of keloids in general and to search for possible treatments.

Prevention of component separation in complex abdominal wall surgery by Botox prehabilitation: a propensity-matched study.

AIM: To facilitate midline fascial closure in complex abdominal wall surgery, component separation techniques (CST) are usually required. However, CST is associated with an enlarged morbidity. Prehabilitation could increase the compliance of the abdominal wall and thereby decrease the necessity of myofascial release. This can be accomplished by administration of botulinum toxin type A (BTA) in the lateral abdominal wall musculature. The aim of this study was to determine the effect of BTA on the subsequent necessity to perform CST in patients with complex abdominal wall hernias. METHODS: Patients with a complex abdominal wall hernia, planned to undergo CST between July 2020 and November 2022 were included. Outcome of procedures with 300U of BTA 4 (2-6) weeks prior to surgery, were retrospectively analyzed by comparison with propensity matched subjects of an historical group. Hernia width difference was assessed by CT and operative details were included. RESULTS: A total of 13 patients with a median hernia width of 12 cm (IQR 9-14, range 24) were prehabilitated with BTA between July 2020 and November 2022. A CST was planned for all, however not required in 6/13 patients (46%) to accomplish midline fascial closure. A mean elongation of lateral abdominal wall musculature of 4.01 cm was seen in patients not requiring CST. Compared to the propensity score matched control group, a 27% reduction (p = 0.08) in the need for CST was observed. CONCLUSION: There is a tendency for decrease of necessity for CST by preoperatively administered BTA in patients with complex abdominal wall defects. Although small, as this study used propensity matched comparison, further exploration of BTA should be encouraged.

Evaluation of long-term function, complications, quality of life and health status after restorative proctocolectomy with ileo neo rectal and with ileal pouch anal anastomosis for ulcerative colitis.

AIM: Restorative surgery after (procto)colectomy with ileo-neorectal anastomosis (INRA) or restorative proctocolectomy with ileal pouch anal anastomosis (RPC) combines cure of ulcerative colitis (UC) with restoration of intestinal continuity. This study aimed to evaluate these two operations. METHOD: Patients having INRA and RPC were matched according to sex, age at onset of UC, age at restorative surgery and duration of follow-up. Patients were included if they were over 18 years of age, had UC confirmed histopathologically and had undergone either operation. Long-term function, anal and neorectal physiology, complications, quality of life (QoL) and health status (HS) were determined. RESULTS: Seventy-one consecutive patients underwent surgery with the intention of having an INRA procedure. This was successfully carried out in 50, and 21 underwent intra-operative conversion to RPC. Median defaecation frequency was 6/24 h. In 11/71 patients reservoir failure occurred and 13/71 developed pouchitis. QoL and HS were comparable to the healthy population. Median follow-up was 6.2 years. These patients were matched with 71 patients who underwent RPC. RPC was successful in all patients. Median defaecation frequency was 8/24 h. Failure occurred in 7/71 patients and 13/71 developed pouchitis. QoL and HS were comparable with the healthy population. Median follow-up was 6.9 years. CONCLUSION: Comparison of INRA and RPC on an intention to treat basis was not considered to be realistic due to the high intra-operative conversion rate and the failures in the INRA group. RPC remains the procedure of choice for restoring intestinal continuity after proctocolectomy for UC.

Honey bee lines selected for high propolis production also have superior hygienic behavior and increased honey and pollen stores.

Honey bees use propolis to defend against invaders and disease organisms. As some colonies produce much more propolis than others, we investigated whether propolis collecting is associated with disease resistance traits, including hygienic behavior and resistance to the parasitic bee mite, Varroa destructor. The three highest (HP) and three lowest propolis-producing (LP) colonies among 36 Africanized honey bee colonies were initially selected. Queens and drones from these colonies were crossed through artificial insemination to produce five colonies of each of the following crosses: HP♀ X HP♂, LP♀ X HP♂, HP♀ X LP♂, and LP♀ X LP♂. Colonies headed by HP♀ X HP♂ queens produced significantly more propolis than those with HP♀ X LP♂ and LP♀ X HP♂ queens and these in turn produced significantly more propolis than those headed by LP♀ X LP♂ queens. The brood cell uncapping rate of the high-propolis-producing colonies in the hygienic behavior test was significantly superior to that of the other groups. The LP X LP group was significantly less hygienic than the two HP X LP crosses, based on the evaluation of the rate of removal of pin-killed pupae. The HP X HP colonies were significantly more hygienic than the other crosses. No significant differences were found in mite infestation rates among the groups of colonies; although overall, colony infestation rates were quite low (1.0 to 3.2 mites per 100 brood cells), which could have masked such effects. Honey and pollen stores were significantly and positively correlated with propolis production.

Rapid method for DNA extraction from the honey bee Apis mellifera and the parasitic bee mite Varroa destructor using lysis buffer and proteinase K.

We developed a rapid method for extraction of DNA from honey bees, Apis mellifera, and from the parasitic bee mite, Varroa destructor. The advantages include fast processing and low toxicity of the substances that are utilized. We used lysis buffer with nonionic detergents to lyse cell walls and proteinase K to digest proteins. We tested whole thorax, thoracic muscle mass, legs, and antennae from individual bees; the mites were processed whole (1 mite/sample). Each thorax was incubated whole, without cutting, because exocuticle color pigment darkened the extraction solution, interfering with PCR results. The procedure was performed with autoclaved equipment and laboratory gloves. For each sample, we used 100 µL lysis buffer (2 mL stock solution of 0.5 M Tris/HCl, pH 8.5, 10 mL stock solution of 2 M KCl, 500 µL solution of 1 M MgCl2, 2 mL NP40, and 27.6 g sucrose, completed to 200 mL with bidistilled water and autoclaved) and 2 µL proteinase K (10 mg/mL in bidistilled water previously autoclaved, as proteinase K cannot be autoclaved). Tissues were incubated in the solutions for 1-2 h in a water bath (62°-68 °C) or overnight at 37 °C. After incubation, the tissues were removed from the extraction solution (lysis buffer + proteinase K) and the solution heated to 92 °C for 10 min, for proteinase K inactivation. Then, the solution with the extracted DNA was stored in a refrigerator (4°-8 °C) or a freezer (-20 °C). This method does not require centrifugation or phenol/chloroform extraction. The reduced number of steps allowed us to sample many individuals/day. Whole mites and bee antennae were the most rapidly processed. All bee tissues gave the same quality DNA. This method, even using a single bee antenna or a single mite, was adequate for extraction and analysis of bee genomic and mitochondrial DNA and mite genomic DNA.

Protein levels and colony development of Africanized and European honey bees fed natural and artificial diets.

Pollen substitute diets are a valuable resource for maintaining strong and health honey bee colonies. Specific diets may be useful in one region or country and inadequate or economically unviable in others. We compared two artificial protein diets that had been formulated from locally-available ingredients in Brazil with bee bread and a non-protein sucrose diet. Groups of 100 newly-emerged, adult workers of Africanized honey bees in Brazil and European honey bees in the USA were confined in small cages and fed on one of four diets for seven days. The artificial diets included a high protein diet made of soy milk powder and albumin, and a lower protein level diet consisting of soy milk powder, brewer's yeast and rice bran. The initial protein levels in newly emerged bees were approximately 18-21 µg/µL hemolymph. After feeding on the diets for seven days, the protein levels in the hemolymph were similar among the protein diet groups (~37-49 µg/µL after seven days), although Africanized bees acquired higher protein levels, increasing 145 and 100% on diets D1 and D2, respectively, versus 83 and 60% in the European bees. All the protein diets resulted in significantly higher levels of protein than sucrose solution alone. In the field, the two pollen substitute diets were tested during periods of low pollen availability in the field in two regions of Brazil. Food consumption, population development, colony weight, and honey production were evaluated to determine the impact of the diets on colony strength parameters. The colonies fed artificial diets had a significant improvement in all parameters, while control colonies dwindled during the dearth period. We conclude that these two artificial protein diets have good potential as pollen substitutes during dearth periods and that Africanized bees more efficiently utilize artificial protein diets than do European honey bees.

The influence of a multidisciplinary team meeting and prehabilitation on complex abdominal wall hernia repair outcomes.

PURPOSE: Surgical site occurrences after transversus abdominis release in ventral hernia repair are still reported up to 15%. Evidence is rising that preoperative improvement of risk factors might contribute to optimal patient recovery. A reduction of complication rates up to 40% has been reported. The aim of this study was to determine whether prehabilitation has a favorable effect on the risk on wound and medical complications as well as on length of stay. METHODS: A retrospective cohort study was performed in a tertiary referral center for abdominal wall surgery. All patients undergoing ventral hernia repair discussed at multidisciplinary team (MDT) meetings between 2015 and 2019 were included. Patients referred for a preconditioning program by the MDT were compared to patients who were deemed fit for operative repair by the MDT, without such a program. Endpoints were patients, hernia, and procedure characteristics as well as length of hospital stay, wound and general complications. RESULTS: A total of 259 patients were included of which 126 received a preconditioning program. Baseline characteristics between the two groups were statistically significantly different as the prehabilitated group had higher median BMI (28 vs 30, p < 0.001), higher HbA1c (41 vs 48, p = 0.014), more smokers (4% vs 25%, p < 0.001) and higher HPW classes due to more patient factors (14% vs 48%, p < 0.001). There were no significant differences in intra-operative and postoperative outcome measures. CONCLUSIONS: This study showed prehabilitation facilitates patients with relevant comorbidities achieving the same results as patients without those risk factors. The indication of a preconditioning program might be effective at the discretion of an MDT meeting. Further research could focus on the extent of such program to assess its value.

Impact of a multidisciplinary team discussion on planned ICU admissions after complex abdominal wall reconstruction.

BACKGROUND: Patients often need admission at an Intensive Care Unit (ICU), immediately after complex abdominal wall reconstruction (CAWR). Lack of ICU resources requires adequate patient selection for a planned postoperative ICU admission. Risk stratification tools like Fischer score and Hernia Patient Wound (HPW) classification may improve patient selection. This study evaluates the decision-making process in a multidisciplinary team (MDT) on justified ICU admissions for patients after CAWR. METHODS: A pre-Covid-19 pandemic cohort of patients, discussed in a MDT and subsequently underwent CAWR between 2016 and 2019, was analyzed. A justified ICU admission was defined by any intervention within the first 24 h postoperatively, considered not suitable for a nursing ward. The Fischer score predicts postoperative respiratory failure by eight parameters and a high score (> 2) warrants ICU admission. The HPW classification ranks complexity of hernia (size), patient (comorbidities) and wound (infected surgical field) in four stages, with increasing risk for postoperative complications. Stages II-IV point to ICU admission. Accuracy of the MDT decision and (modifications of) risk-stratification tools on justified ICU admissions were analyzed by backward stepwise multivariate logistic regression analysis. RESULTS: Pre-operatively, the MDT decided a planned ICU admission in 38% of all 232 CAWR patients. Intra-operative events changed the MDT decision in 15% of all CAWR patients. MDT overestimated ICU need in 45% of ICU planned patients and underestimated in 10% of nursing ward planned patients. Ultimately, 42% went to the ICU and 27% of all 232 CAWR patients were justified ICU patients. MDT accuracy was higher than the Fischer score, HPW classification or any modification of these risk stratification tools. CONCLUSION: A MDT's decision for a planned ICU admission after complex abdominal wall reconstruction was more accurate than any of the other risk-stratifying tools. Fifteen percent of the patients experienced unexpected operative events that changed the MDT decision. This study demonstrated the added value of a MDT in the care pathway of patients with complex abdominal wall hernias.

Rapid morphological changes in populations of hybrids between Africanized and European honey bees.

African honey bees, introduced to Brazil in 1956, rapidly dominated the previously introduced European subspecies. To better understand how hybridization between these different types of bees proceeded, we made geometric morphometric analyses of the wing venation patterns of specimens resulting from crosses made between Africanized honey bees (predominantly Apis mellifera scutellata) and Italian honey bees (A. mellifera ligustica) from 1965 to 1967, at the beginning of the Africanization process, in an apiary about 150 km from the original introduction site. Two virgin queens reared from an Italian parental were instrumentally inseminated with semen from drones from an Africanized parental. Six F(1) queens from one of these colonies were open mated with Africanized drones. Resultant F(1) drones were backcrossed to 50 Italian and 50 Africanized parental queens. Five backcross workers were collected from each of eight randomly selected colonies of each type of backcross (N = 5 bees x 8 colonies x 2 types of backcrosses). The F1 progeny (40 workers and 30 drones) was found to be morphologically closer to the Africanized than to the European parental (N = 20 drones and 40 workers, each); Mahalanobis square distances = 21.6 versus 25.8, respectively, for the workers, and 39.9 versus 46.4, respectively, for the drones. The worker progenies of the backcrosses (N = 40, each) were placed between the respective parental and the F(1) progeny, although closer to the Africanized than to the Italian parentals (Mahalanobis square distance = 6.2 versus 12.1, respectively). Consequently, the most common crosses at the beginning of the Africanization process would have generated individuals more similar to Africanized than to Italian bees. This adds a genetic explanation for the rapid changes in the populational morphometric profile in recently colonized areas. Africanized alleles of wing venation pattern genes are apparently dominant and epistatic.

First report of sacbrood virus in honey bee (Apis mellifera) colonies in Brazil.

Sacbrood disease, an affliction of honey bees (Apis mellifera) characterized by brood that fails to pupate and subsequently dies, is an important threat to honey bee health. The disease is caused by the sacbrood virus (SBV), a positive-, single-stranded RNA virus in the order Picornavirales. Because of the economic importance of honey bees for both pollination and honey production, it is vital to understand and monitor the spread of viruses such as SBV. This virus has been found in many places across the globe, including recently in some South American countries, and it is likely that it will continue to spread. We performed a preliminary study to search for SBV in two apiaries of Africanized honey bees in the State of São Paulo, Brazil, using RT-PCR and Sanger sequencing and found the first evidence of SBV in honey bee colonies in Brazil. The virus was detected in larvae, foraging and nurse bees from two colonies, one of which had symptoms of sacbrood disease, at the beginning of the winter season in June 2011. No SBV was found in samples from nine other nearby colonies.

Microalbuminuria is not a valuable marker for relapse in Crohn's disease.

BACKGROUND: Previous reports correlated microalbuminuria with disease activity in patients with Crohn's disease (CD). The aim of the present study is to determine the value of microalbuminuria as a marker for relapses in quiescent CD. METHODS: In a 1-year prospective maintenance trial with oral budesonide in patients with CD in remission, microalbuminuria was measured at randomization, after 2, 6 and 12 months, plus at the time of a relapse. The association of microalbuminuria with the course of disease was analyzed with logistic regression analysis. Time-dependent Cox regression was undertaken to study the association between microalbuminuria and relapse. RESULTS: We included a total of 139 patients. At randomization, microalbuminuria was present in 8 patients. During a 1-year follow-up, 29 patients relapsed and in 11% (3/29), microalbuminuria was present during the relapse. We found no statistically significant association between microalbuminuria and relapse (odds ratio 0.92, 95% confidence interval (CI) 0.76-1.13). Time-dependent Cox regression analysis also revealed no statistical predictive value for microalbuminuria (hazard ratio 1.29, 95% CI 0.37-4.39, p = 0.68). CONCLUSION: Microalbuminuria was moderately prevalent in quiescent CD patients, but it could not be associated with disease characteristics or the type of medication before randomization, nor as a predictor for relapses.

Therapy failure following selection of enfuvirtide-resistant HIV-1 in cerebrospinal fluid.

We report the selection of enfuvirtide-resistant human immunodeficiency virus type 1 in cerebrospinal fluid, resulting in subsequent loss of viral suppression in the plasma. This case report emphasizes the potential danger of low-level penetration of entry inhibitors into the central nervous system.

Translocation t(14;18) in B cell lymphomas as a cause for defective immunoglobulin production.

Although follicle center cell (FCC) lymphomas represent mature B cells, a considerable percentage do not have detectable Ig production. We have used Southern blotting and the polymerase chain reaction (PCR) to study the involvement of translocations t(14;18) and t(8;14) in causing defective Ig production in 16 Ig- FCC-derived lymphomas and three Ig- B cell acute lymphoblastic leukemias. In 6 of 19 cases, a t(14;18) was present with the other allele either deleted or in germline. In two cases a t(14;18) and a t(8;14) affected both Ig alleles, as confirmed by karyotyping. In two other cases, rearrangement of both bcl-2 on chromosome 18 and c-myc on chromosome 8 were found as well. Although cytogenetic proof was not available, the latter was probably involved in t(8;14). Restriction map analysis of one more case showed rearrangement on the pseudo-JH3 gene on one allele and t(14;18) on the other. Thus, in 11 of 19 cases, defective Ig H chain production could be explained by the inactivation of both Ig H chain genes due to translocation of one allele, in combination with deletions or defective rearrangements of the other allele. In contrast, in 28 of 30 Ig+ lymphomas, one functional Ig H chain allele was found, either in, or not in, combination with t(14;18). In two cases a single rearranged Ig H chain allele was found in combination with rearrangement of bcl-2. No comigration of the single Ig rearrangement with bcl-2, however, was found both by Southern blotting and PCR, suggesting a variant bcl-2 translocation, which leaves the Ig H chain allele functionally intact.