Fracture risk following bariatric surgery: a systematic review and meta-analysis.

Bariatric surgery may negatively impact bone health. We aimed to compare fracture risk following bariatric surgery by type (malabsorptive, restrictive), or to non-surgical weight loss, or to controls with obesity. We systematically searched four databases from inception until October 2020. We included observational and interventional studies on adults. We screened articles and abstracted data in duplicate and independently and assessed the risk of bias. We conducted random-effects model meta-analyses (Review Manager v5.3), to calculate the relative risk of any or site-specific fracture (CRD42019128536). We identified four trials of unclear-to-high risk of bias and 15 observational studies of fair-to-good quality. Data on fracture risk following bariatric surgery compared to medical weight loss is scarce and limited by the small number of participants. In observational studies, at a mean/median post-operative follow-up > 2 years, the relative risk of any fracture was 45% (p < 0.001) and 61% (p = 0.04) higher following malabsorptive procedures compared to obese controls and restrictive procedures, respectively, with moderate to high heterogeneity. Site-specific relative fracture risk (hip and wrist) was one- to two-folds higher post malabsorptive procedures compared to obese controls or restrictive procedures. The risks of any and of site-specific fracture were not increased following restrictive procedures compared to obese controls. Fracture risk seems to increase following malabsorptive bariatric surgeries, at a mean/median follow-up > 2 years. The risk is not increased with restrictive surgeries. The available evidence has several limitations. A prospective and rigorous long-term follow-up of patients following bariatric surgery is needed for a better assessment of their fracture risk with aging.

Residence time distribution studies using radiotracers in a lab-scale distillation column: Experiments and modeling.

The radiotracer's residence time distribution (RTD) is an important study of the performance of industrial process reactors.The application of radiotracers is the method used to diagnose the functioning of packed distillation columns. This paper presents the results of an experiment carried out using the Technitium-99 (Mo99) radiotracer to determine the RTD in a laboratory-scale packed distillation column.The concentration of the radiotracer is monitored using eight scintillation detectors.The obtained data is treated for background correction, radioactive decay correction, starting point correction, filtering, and data extrapolation. After this preprocessing, two mathematical models are investigated on this data using International Atomic Energy Agency (IAEA) RTD software. The parameters of each model are optimized in oder to calculate the value of the RTD, and to determine the model which gives the best match with the experimental data. The appropriate model is than selected. Consequenly the one with the best match, is used to deduce the crucial parameter RTD in this experiment.

Alveolar and intraparenchymal proteasome in sarcoidosis.

BACKGROUND: In sarcoidosis, an antigen specific immune response is a putative mechanism, resulting in granulomatous inflammation. Since the proteasome is involved in antigen presentation, alterations in the alveolar and parenchymal proteasomal system may be a feature of sarcoidosis. OBJECTIVES: To explore the role of proteasomes and immunoproteasomes in sarcoidosis. METHODS: Total proteasome concentration and activity was assessed in bronchoalveolar lavage (BAL) supernatant obtained from sarcoidosis patients (n = 67) and healthy controls (n = 18) using ELISA and cleavage of specific fluorogenic substrates (±epoxomicin), respectively. Immunohistochemistry of lung tissue sections and immunocytochemistry of BAL macrophages for immunoproteasome was performed in sarcoidosis patients and controls. RESULTS: Proteasome was present in BAL supernatants of all sarcoidosis patients. In sarcoidosis, abundant immunoproteasome staining was seen in pneumocytes type II and granulomas. Total proteasome concentration was greater in active sarcoidosis, stages II (101 ng/ml ± 79; p = 0.009) and III (119 ng/ml ± 66; p = 0.012), than in inactive sarcoidosis or in healthy controls (35 ng/ml ± 34). In the absence of epoxomicin, all fluorogenic substrates were hydrolyzed by BAL supernatant of sarcoidosis patients and controls. CONCLUSIONS: Patients with active sarcoidosis but not healthy controls demonstrate immunoproteasome in the lung tissue and in granulomas. Thus, the putative immune response in sarcoidosis may be mediated or sustained by the proteasomal system.

Mapping rare erythrocyte phenotypes in morocco: a tool to overcome transfusion challenges.

The aim of this research is to search for the distribution of blood groups in all the regions of Morocco. This study, done for the first time, aimed to provide the frequency of the Rhesus system and Kell (K) in more than 55000 blood donors from nine different regions around the country. In addition, the frequency of the Cellano, Duffy, Kidd, and MNS blood antigens was searched for 500 blood donors from the Rabat's region. Frequency of blood donors with rare blood groups was characterized for the first time in the country and compared to results found from other populations.

Hepatitis B in Moroccan blood donors: a decade trend of the HBsAg prevalence in a resources limited country.

OBJECTIVES: To calculate the hepatitis B surface antigen (HBsAg) reactive rate for 2011 blood donors (BD) across Morocco. In addition, to monitor the profile of donors bearing the HBsAg during 2000 and 2011, we calculated the percentage of the prevalence in both sexes, in different age groups and in first-time replacement and regular BD from the Rabat Regional Blood Transfusion Centre. BACKGROUND: Hepatitis B is a viral infection that spreads through blood and other biological fluids. The hepatitis B virus remains one of the most common serious complications of transfusion. No information exists on the real prevalence of hepatitis B in Moroccan BD. METHODS: For the 2011 national HBsAg reactive rate, the percentage was calculated based on enzyme-linked immunosorbent assay (ELISA) results of the 232 190 blood donations collected around the country. For the Rabat blood Centre, we calculated the hepatitis B sero-prevalence from donations made at the donors' suite during 2000 and 2011. RESULTS: The national prevalence of HBsAg was 1·34%. The HBsAg variations among different regions was between 0·43 and 2·86%. The Rabat donors' suite hepatitis B prevalence decreased from 2·47% in 2000 to 0·91% in 2011 (P < 0·001). In both years, family/replacement donors were found as safe as first-time BD and female donors were the safest. CONCLUSIONS: These results, presented for the first time in the country, mapped the hepatitis B distribution across Morocco in a healthy population. The findings of this study could be of great importance in setting up strategies for the recruitment of the BD and keeping blood safety at the highest level.

Blood donation in Morocco: a 20-year retrospective study of blood collection in the Rabat blood centre.

OBJECTIVES: We trace the history of blood donors and the recruitment strategies developed between 1988 and 2008 in the regional blood transfusion centre of Rabat. Beside, we draw a distribution map of the blood donors' population in Morocco during the year 2008. BACKGROUND: Limited resource countries face considerable obstacles to ensuring a safe blood supply and safe blood transfusions. Many countries used and some of them still depend on replacement blood donors. METHODS: Data published in this article had been collected from the CRTS of Rabat archives and reports. Data from all the 16 regional blood transfusion centres were collected from the report annually presented by the different regions. RESULTS: We found that during the 20 years period studied, the number of blood units collected by Rabat recorded many fluctuations. In the mean time, many measures were taken to promote the recruitment of voluntary blood donors. The proportion of these later jumped from 16·55% in 1988 to reach almost 80% in 2008. Beside, the whole country's blood collection map for the year 2008 showed that 190 504 of whole blood units were collected. This means that there are only six donations per 1000 people. CONCLUSION: This is the first study conducted in Morocco that provided detailed information on ongoing trends in blood donor profiles. The creation and development of new mobile drive units and maintaining them over time was the key to increase the collection of blood units from voluntary, non-remunerated blood donors.

Distinct proteasome subpopulations in the alveolar space of patients with the acute respiratory distress syndrome.

There is increasing evidence that proteasomes have a biological role in the extracellular alveolar space, but inflammation could change their composition. We tested whether immunoproteasome protein-containing subpopulations are present in the alveolar space of patients with lung inflammation evoking the acute respiratory distress syndrome (ARDS). Bronchoalveolar lavage (BAL) supernatants and cell pellet lysate from ARDS patients (n = 28) and healthy subjects (n = 10) were analyzed for the presence of immunoproteasome proteins (LMP2 and LMP7) and proteasome subtypes by western blot, chromatographic purification, and 2D-dimensional gelelectrophoresis. In all ARDS patients but not in healthy subjects LMP7 and LMP2 were observed in BAL supernatants. Proteasomes purified from pooled ARDS BAL supernatant showed an altered enzyme activity ratio. Chromatography revealed a distinct pattern with 7 proteasome subtype peaks in BAL supernatant of ARDS patients that differed from healthy subjects. Total proteasome concentration in BAL supernatant was increased in ARDS (971 ng/mL ± 1116 versus 59 ± 25; P < 0.001), and all fluorogenic substrates were hydrolyzed, albeit to a lesser extent, with inhibition by epoxomicin (P = 0.0001). Thus, we identified for the first time immunoproteasome proteins and a distinct proteasomal subtype pattern in the alveolar space of ARDS patients, presumably in response to inflammation.

Alanine transaminase level in a healthy population in Morocco.

A little is known about the prevalence of elevated alanine transaminase in a Moroccan healthy population. Our aim was to search for the upper limit of normal alanine transaminase in the blood donors and then to apply the upper limit of normal alanine found in the population so as to assess the prevalence of subjects with abnormal transaminase level. We then, investigated for factors associated with increased level of transaminase in our population. This study was carried out on 14071 blood donors, (74.1% of men and 25.9% female) aged between 18 to 60 years, randomly chosen. Serum transaminase activity was measured using on IEMS Reader, Labsystems. Hepatitis B and C were performed by ELISA. The upper limit of normal transaminase found were 64 for men and 52 for women. Consequently, 2.08% blood donors had an abnormal level of transaminase. Follow up results revealed that drug was the first cause of elevated transaminase in our cohort followed by diet and alcohol consumption. One seroconversion for hepatitis C was identified. In conclusion, this study showed that even though there is an evident lack of efficiency in using alanine aminotransferase testing qualifying blood donors in our country, preventing viral potential transmission through transfusions was possible.

Sex, age and ABO blood groups in chemotherapy-induced oropharyngeal mucositis.

AIM: The contribution of host genetic factors in oropharyngeal mucositis is not fully understood. Therefore, we conducted this study to determine possible associations of age, sex, underlying disease, type of chemotherapy and ABO blood group antigens with the risk of chemotherapy-induced oropharyngeal mucositis. METHODS: A total of 641 patients (395 boys and 246 girls; mean age 6.82+/-4.08 years) treated by standard chemotherapy for different type of malignancies were enrolled in the study. Mucositis was scored using the WHO scale. RESULTS: Oropharyngeal mucositis was found in 65.4% of our population. Patients with hematological malignancies (RR=1.87; 95% CI 1.33-2.67; P<0.0001) and under antimetabolities drugs (RR=1.88; 95% CI 1.33-2.63; P<0.0001) were associated with increased risk of oropharyngeal mucositis. Also, patients with blood group O were at higher risk (RR=2.86; 95% CI 2.03-4.02; P<0.0001) compared to patients with blood type A (RR= 0.47; 95% CI 0.33-0.66; P<0.0001) and blood type B (RR=0.59; 95% CI 0.38-0.91; P= 0.01). No relationship was found between oropharyngeal mucositis and age or sex. CONCLUSIONS: To our knowledge this is the first report demonstrating an association between ABO blood group and oropharyngeal mucositis. Further investigations are needed for a better understanding of this relationship.

Transnasal small-caliber esophagogastroduodenoscopy for preoperative evaluation of the high-risk morbidly obese patient.

BACKGROUND: Esophagogastroduodenoscopy (EGD) is an important facet of the preoperative evaluation for bariatric surgery. Morbidly obese patients are at high risk for airway complications during this procedure, and an attractive alternative is transnasal EGD. This report describes a series of patients evaluated successfully using this technique. METHODS: All patients undergoing preoperative transnasal small-caliber EGD for morbid obesity surgery between September 2004 and June 2005 at a Veterans Affairs Hospital were included in the analysis. The variables assessed were the adequacy of the examination, patient tolerance, the need for sedation, and the ability to perform interventions. RESULTS: The study enrolled 25 patients (17 men and 8 women) with an average age of 55 years (range, 44-63 years) and an average body mass index (BMI) of 47 kg/m2 (range, 38-69 kg/m2). All the patients met the 1991 National Institutes of Health (NIH) Consensus Conference Criteria for bariatric surgery and were undergoing preoperative evaluation. The most common comorbidities were hypertension (82%), diabetes mellitus (80%), and obstructive sleep apnea (68%). All 25 patients had successful cannulation of the duodenum's second portion with excellent tolerance. There were no sedation requirements for 23 (92%) of the 25 patients. Significant pathology was found in 14 (56%) of the 25 patients, including hiatal hernia (28%), gastritis (16%), esophageal intestinal metaplasia (16%), esophagitis (12%), gastric polyps (8%), gastric ulcer (4%) and esophageal varices (4%). Biopsies were indicated for 12 patients and successful for all 12 (100%). CONCLUSION: Transnasal small-caliber EGD is a feasible and safe alternative to conventional EGD for the preoperative evaluation of patients undergoing bariatric surgery. It requires minimal to no sedation in a population at high risk for complications in this setting. In addition, this technique is effective in identifying pathology that requires preoperative treatment and offers a complete examination with biopsy capabilities. This technique should be considered for all morbidly obese patients at high risk for airway compromise during EGD.

The impact of preoperative weight loss in patients undergoing laparoscopic Roux-en-Y gastric bypass.

BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGBP) is a widely performed bariatric operation. Preoperative factors that predict successful outcomes are currently being studied. The goal of this study was to determine if preoperative weight loss was associated with positive outcomes in patients undergoing LRYGBP. METHODS: A retrospective analysis was performed of all patients undergoing LRYGBP at our institution between July 2002 (when a policy of preoperative weight loss was instituted) and August 2003. Outcome measures evaluated at 1 year postoperatively included percent excess weight loss (EWL) and correction of co-morbidities. Statistical analysis was performed by multiple linear regression. P<0.05 was considered significant. RESULTS: The study included 90 subjects. Initial BMI ranged from 35.4 to 63.1 (mean 48.1). Preoperative weight loss ranged from 0 to 23.8% (mean 7.25). At 12 months, postoperative EWL ranged from 40.4% to 110.9 % (mean 74.4%). Preoperative loss of 1% of initial weight correlated with an increase of 1.8% of postoperative EWL at 1 year. In addition, initial BMI correlated negatively with EWL, so that an increase of 1 unit of BMI correlated with a decrease of 1.34% of EWL. Finally, preoperative weight loss of >5% correlated significantly with shorter operative times by 36 minutes. Preoperative weight loss did not correlate with postoperative complications or correction of co-morbidities. CONCLUSIONS: Preoperative weight loss resulted in higher postoperative weight loss at 1 year and in shorter operative times with LRYGBP. No differences in correction of co-morbidities or complication rates were found with preoperative weight loss in this study. Preoperative weight loss should be encouraged in patients undergoing bariatric surgery.

Targeted deletion of 5'HS1 and 5'HS4 of the beta-globin locus control region reveals additive activity of the DNaseI hypersensitive sites.

The mammalian beta-globin locus is a multigenic, developmentally regulated, tissue-specific locus from which gene expression is regulated by a distal regulatory region, the locus control region (LCR). The functional mechanism by which the beta-globin LCR stimulates transcription of the linked beta-like globin genes remains unknown. The LCR is composed of a series of 5 DNaseI hypersensitive sites (5'HSs) that form in the nucleus of erythroid precursors. These HSs are conserved among mammals, bind transcription factors that also bind to other parts of the locus, and compose the functional components of the LCR. To test the hypothesis that individual HSs have unique properties, homologous recombination was used to construct 5 lines of mice with individual deletions of each of the 5'HSs of the endogenous murine beta-globin LCR. Here it is reported that deletion of 5'HS1 reduces expression of the linked genes by up to 24%, while deletion of 5'HS4 leads to reductions of up to 27%. These deletions do not perturb the normal stage-specific expression of genes from this multigenic locus. In conjunction with previous studies of deletions of the other HSs and studies of deletion of the entire LCR, it is concluded that (1) none of the 5'HSs is essential for nearly normal expression; (2) none of the HSs is required for proper developmental expression; and (3) the HSs do not appear to synergize either structurally or functionally, but rather form independently and appear to contribute additively to the overall expression from the locus.

Deletions within the mouse beta-globin locus control region preferentially reduce beta(min) globin gene expression.

The mouse beta-globin gene cluster is regulated, at least in part, by a locus control region (LCR) composed of several developmentally stable DNase I hypersensitive sites located upstream of the genes. In this report, we examine the level of expression of the beta(min) and beta(maj) genes in adult mice in which HS2, HS3, or HS5,6 has been either deleted or replaced by a selectable marker via homologous recombination in ES cells. Primer extension analysis of RNA extracted from circulating reticulocytes and HPLC analysis of globin chains from peripheral red blood cells revealed that all mutations that reduce the overall output of the locus preferentially decrease beta(min) expression over beta(maj). The implications of these findings for the mechanism by which the LCR controls expression of the beta(maj) and beta(min) promoters are discussed.

Beta-globin YAC transgenes exhibit uniform expression levels but position effect variegation in mice.

Expression of a construct integrated at different genomic locations often varies because of position effects that have been subcategorized as stable (decreased level of expression) and variegating (decreased proportion of expressing cells). It is well established that locus control regions (LCRs) generally overcome position effects in transgenes. However, whether stable and variegated position effects are equally overcome by an intact LCR has not been determined. We report that single-copy yeast artificial chromosome transgenes containing an unmodified human beta -globin locus were not subject to detectable stable position effects but did undergo mild to severe variegating position effects at three of the four non-centromeric integration sites tested. We also find that, at a given integration site, the distance and the orientation of the LCR relative to the regulated gene contributes to the likelihood of variegating position effects, and can affect the magnitude of its transcriptional enhancement. DNase I hypersensitive site (HSS) formation varies with the proportion of expressing cells, not the level of gene expression, suggesting that silencing of the transgene is associated with a lack of HSS formation in the LCR region. We conclude that transcriptional enhancement and variegating position effects are caused by fundamentally different but inter-dependent mechanisms.

Site-specific chromosomal integration in mammalian cells: highly efficient CRE recombinase-mediated cassette exchange.

Expression of experimental constructs in mammalian cells or transgenic animals is difficult to control because it is markedly influenced by position effects. This has limited both the analysis of cis -DNA regulatory elements for transcription and replication, and the physiological analysis of proteins expressed from transgenes. We report here two new methods based on the concept of recombinase-mediated cassette exchange (RMCE) to perform site-specific chromosomal integration. The first method permits the exchange of a negative selectable marker pre-localized on the chromosome with a transgene via a CRE-mediated double recombination between inverted Lox sites. Integration efficiency is close to 100 % of negatively selected mouse erythroleukemia cells and ranges from 10 to 50 % in embryonic stem cells. The second method allows RMCE with no selection at all except for cells that have taken up plasmid transiently. While less efficient, this technique permits novel experimental approaches. We find that integration of a transgene at a given genomic site leads to reproducible expression. RMCE should be useful to develop artificial genetic loci that impart specific and reproducible regulation of transgenes in higher eukaryotes. This should facilitate the analysis of cis -regulatory DNA elements governing expression and position effects, improve our control over the physiological effects of transgenes, and accelerate the development of animal models for complex human diseases.

Anti-beta s-ribozyme reduces beta s mRNA levels in transgenic mice: potential application to the gene therapy of sickle cell anemia.

Our current strategy for gene therapy of sickle cell anemia involves retroviral vectors capable of transducing "designer" globin genes that code for novel anti-sickling globins (while resisting digestion by a ribozyme), coupled with the expression of a hammerhead ribozyme that can selectively cleave the human beta s mRNA. In this report, we have tested in vivo an anti-beta s hammerhead ribozyme embedded within a cDNA coding for the luciferase reporter gene driven by the human beta-globin promoter and hyper-sensitive sites 3 and 4 of the locus control region. We have created mice transgenic for this luciferase-ribozyme construct and bred the ribozyme transgene into mice that were already transgenic for the human beta s gene. We then measured expression of the beta s transgene at the protein and RNA levels by HPLC and primer extension. The presence of the ribozyme was associated with a statistically significant reduction in the level of beta s mRNA in spleen stress reticulocytes (from 60.5 +/- 4.1% to 52.9 +/- 4.2%) and in the percentage of beta s globin chains in very young mice (from 44.5 +/- 0.6% to 40.8 +/- 0.7%). These results demonstrate that it is possible to decrease the concentration of beta s chains and mRNA with the help of a hammerhead ribozyme. While the enormous amount of globin mRNA in reticulocytes is a challenge for ribozyme technology, the exquisite dependence of the delay time for formation of Hb S nuclei on the concentration of Hb S in red blood cells suggests that even a modest reduction in Hb S concentration would have therapeutic value.

Enhancer-dependent transcriptional oscillations in mouse erythroleukemia cells.

By using recombinase-mediated cassette exchange, a method that allows integration of single copies of different constructs at the same predetermined chromosomal location, several expression cassettes have been integrated at a randomly chosen locus in the genome of mouse erythroleukemia cells. The cassettes studied contain the human beta-globin promoter fused to lacZ coding sequences either alone or linked to DNase I-hypersensitive site HS2, HS3, or HS234 (a large locus control region fragment containing HS2, HS3, and HS4) of the human beta-globin locus control region. Analysis of expression of these cassettes revealed mosaic expression patterns reminiscent of, but clearly different from, position effect variegation. Further investigations demonstrated that these mosaic expression patterns are caused by dynamic activation and inactivation of the transcription unit, resulting in oscillations of expression. These oscillations occur once in every few cell cycles at a rate specific for the enhancer present at the locus. DNase I sensitivity studies revealed that the chromatin is accessible and that DNase-hypersensitive sites were present whether or not the transcription unit is active, suggesting that the oscillations occur between transcriptionally competent and transcriptionally active chromatin conformations, rather than between open and closed chromatin conformations. Treatment of oscillating cells with trichostatin A eliminates the oscillations only after the cells have passed through late G1 or early S, suggesting that these oscillations might be caused by changes in histone acetylation patterns.