Inhibitory control as a potential treatment target for obesity.

OBJECTIVES: Strong reward responsiveness to food and insufficient inhibitory control are thought to be implicated in the development and maintenance of obesity. This narrative review addresses the role of inhibitory control in obesity and weight loss, and in how far inhibitory control is a promising target for weight loss interventions. METHODS: PubMed, Web of Science, and Google Scholar were searched for papers up to May 2021. 41 papers were included. RESULTS: Individuals with obesity have poorer food-specific inhibitory control, particularly when hungry, and less concurrent activation of inhibitory brain areas. Moreover, this was strongly predictive of future weight gain. More activation of inhibitory brain areas, on the other hand, was predictive of weight loss: individuals with successful weight loss initially show inhibitory brain activity comparable to that of normal weight individuals. When successful weight maintenance is achieved for at least 1 year, this inhibitory activity is further increased. Interventions targeting inhibitory control in obese individuals have divergent effects. Firstly, food-specific inhibitory control training is particularly effective for people with low inhibitory control and high BMI. Secondly, neuromodulation paradigms are rather heterogeneous: although rTMS to the left dorsolateral prefrontal cortex induced some weight-loss, multiple sessions of tDCS reduced food consumption (desire) and induced weight loss in two thirds of the papers. Thirdly, neurofeedback results in successful upregulation of brain activity and connectivity, but occasionally leads to increased food intake. In conclusion, inhibitory control is implicated in obesity. It can be targeted to promote weight loss although major weight losses have not been achieved.

A total cost perspective of type 1 and 2 diabetes mellitus in two South African medical schemes servicing the public healthcare sector.

BACKGROUND: Diabetes is increasingly becoming a public health concern in South Africa (SA). There are limited available data on the costs of diabetes. OBJECTIVES: To provide a total cost perspective of diabetes using medical scheme claims data from two SA medical schemes servicing the public healthcare sector in 2015 and 2016. METHODS: We analysed data from 2 363 diabetes patients. Direct diabetes care costs included medication, consumables, hospitalisation and routine laboratory tests. Indirect costs were calculated by allocating economic costs related to disability-adjusted life years. RESULTS: The mean (standard deviation) age was 65.8 (13.4) years and women comprised 51% of the group. Hospitalisation (64.7% in 2015 and 65.5% in 2016) and medication (31.0% in 2015 and 21.1% in 2016) contributed the most to total direct costs. Total direct diabetes care costs mounted to ZAR2 452 per patient in 2015 and ZAR2 486 in 2016. Indirect costs were ZAR17 223 per patient in 2015 and ZAR18 711 in 2016. When direct and indirect costs were combined, the costs accrued to ZAR27.9 billion (ZAR19 675 per patient) in 2015 and ZAR29.9 billion (ZAR21 197 per patient) in 2016, representing 0.688% and 0.689% of the SA gross domestic product over the 2 years, respectively. CONCLUSIONS: Diabetes and its associated costs hold significant implications for the healthcare sector and the country's economy. Large numbers of diabetic individuals remain undiagnosed and the true costs of diabetes might even be higher.

A multimodal prehabilitation program in high-risk patients undergoing elective resection for colorectal cancer: A retrospective cohort study.

AIM: Up to 50% of the patients experience complications after colorectal cancer (CRC) surgery. Improved preoperative physical and nutritional status can enhance clinical outcomes and reduce postoperative complications. This retrospective, single-center, observational cohort study assessed the impact of a four-week multimodal prehabilitation program on postoperative complications, unplanned readmissions, length of stay, and mortality in elective high-risk CRC patients. METHOD: Elective high-risk CRC patients, defined as ASA ≥3 or ≥65yr, who attended the multimodal prehabilitation program (prehabilitation-group) were compared to a historical cohort receiving standard care (control-group). Differences in outcomes between these groups were tested using Fisher's Exact and Mann-Whitney U test. To adjust for confounding, multivariate logistic regression analysis was performed. The main study outcome was the occurrence of postoperative complications. Secondary outcomes included unplanned readmissions, length of hospital stay, and mortality. RESULTS: 351 patients were included (n = 275 control-group, n = 76 prehabilitation-group). The complication rate was lower in the prehabilitation group compared to the control group, 26.3% (n = 20) versus 40% (n = 110) (p = .032). There were fewer unplanned readmissions in the prehabilitation group compared to the control group, 5.3% (n = 4) versus 16.4% (n = 45), p = .014. Median hospital days of stay was 1 day shorter for the prehabilitation-group (p = .004), mortality did not significantly differ between the groups. CONCLUSION: This study shows that the used multimodal prehabilitation program leads to a reduction of medical postoperative complications, unplanned readmissions, and shortens the median hospital stay compared with standard care in high-risk CRC patients undergoing elective CRC surgery.

C-reactive protein as a predictor of severity of appendicitis.

BACKGROUND: Complex (perforated or gangrenous) appendicitis has a high rate of morbidity in South Africa. METHOD: The study retrospectively reviewed results from January 2013 to December 2015 at Paarl Hospital in the Western Cape province. All patients who had their appendices surgically removed due to suspected appendicitis and who had preoperative results for CRP and WCC were included. Using the area under the Receiver Operated Characteristics curve we compared the inflammatory markers of 2 groups with histologically proven appendicitis: those with complex (perforated or gangrenous appendix) and those with uncomplicated appendicitis (inflamed appendix). Youden's J statistic was used to determine the optimal cut-off value above which complex appendicitis would be the most likely diagnosis. RESULTS: A total of 591 patients were identified, 385 had results for both WCC and CRP. CRP (AUC 72%) proved to be a fair and WCC (AUC 58%) a poor predictor of complex appendicitis. Cut-off values for CRP and WCC were found to be 215 mg/l and 16.80 109 cells/l respectively. At these threshold values CRP (sensitivity 51.4%, specificity 85.7%, p-value < 0.001, positive predictive value 80.2%, negative predictive value 61%, positive likelihood ratio 3.6 and diagnostic odds ratio 6.35) proved to be much better than WCC (sensitivity 43%, specificity 73.8%, p-value = 0.022, positive predictive value 64.9%, negative predictive value 53.4%, positive likelihood ratio 1.64 and diagnostic odds ratio 2.11) in predicting complex appendicitis. CONCLUSION: CRP is superior to WCC in the differentiation between uncomplicated and complex appendicitis. Using a cut-off value of CRP 215 mg/l is statistically significant in diagnosing complex appendicitis. This value should be used cautiously as many more studies are needed to confirm these findings.

Altruistic donor triggered domino-paired kidney donation for unsuccessful couples from the kidney-exchange program.

Between January 2000 and July 2009, 132 individuals inquired about altruistic kidney donation to strangers. These donors were willing to donate to genetically and emotionally unrelated patients. Some altruistic donors wished to donate to a specific person, but most wished to donate anonymously. In domino-paired donation, the altruistic donor donates to the recipient of an incompatible couple; the donor of that couple (domino-donor) donates to another couple or to the waiting list. In contrast to kidney-exchange donation where bilateral matching of couples is required, recipient and donor matching are unlinked in domino-paired donation. This facilitates matching for unsuccessful couples from the kidney-exchange program where blood type O prevails in recipients and is under-represented in donors. Fifty-one altruistic donors (39%) donated their kidney and 35 domino-donors were involved. There were 29 domino procedures, 24 with 1 altruistic donor and 1 domino-donor, 5 with more domino-donors. Eighty-six transplantations were performed. Donor and recipient blood type distribution in the couples limited allocation to blood type non-O waiting list patients. The success rate of domino-paired donation is dependent on the composition of the pool of incompatible pairs, but it offers opportunities for difficult to match pairs that were unsuccessful in the kidney-exchange program.

[Combined vision and hearing impairment: in an estimated 30,000-35,000 people aged 55 years or over in The Netherlands]. / Gecombineerde visus- en gehoorbeperking: naar schatting bij 30,000-35,000 55-plussers in Nederland.

OBJECTIVE: To determine the number of older people with acquired dual sensory impairment (DSI) in The Netherlands. DESIGN: Combination of studies in the general population and in relevant subpopulations. METHOD: Eight databases derived from recent studies on older persons with vision and hearing data on Dutch subjects aged 55 years or over were selected for further analysis. The measurement methods included self-reports, clinical measurements and observations. The prevalences of DSI were calculated for the general population, the non-institutionalised population, and subgroups such as older people in nursing homes and homes for the elderly. The calculated prevalences were extrapolated to the overall Dutch population. RESULTS: For the non-institutionalised population of 55 years and older, the prevalences of acquired DSI in two different data sets were 0.4% (95% CI: 0.2-0.6) and 0.6% (95% CI: 0.3-0.8), respectively. Among the inhabitants of homes for the elderly these percentages were 5.4% (95% CI: 0.9-9.9) and 5.5% (95% CI: 3.8-7.2), and in nursing homes they were 12.7% (95% CI: 9.7-15.7) and 16.7% (95% CI: 14.6-18.8). Acquired DSI was most common in persons 85 years of age and older. It was estimated that the number of people aged 55 years and over with acquired DSI in The Netherlands is 30,000 to 35,000. CONCLUSION: DSI is particularly a problem of the oldest old. An integrated approach to the visual and hearing problems of these subjects is essential.

[Favourable results of the first 2 years of the Dutch paired, living donor, kidney exchange programme]. / Gunstige resultaten van de eerste 2 jaar van het Nederlandse gepaarde-donorruilprogramma voor nierdonatie met een levende donor.

OBJECTIVE: To assess the results of the paired, living donor, kidney exchange protocol in the Netherlands. DESIGN: Descriptive. METHODS: In January 2004, all 7 Dutch kidney transplantation centres implemented a paired, living donor, kidney exchange protocol for donor-recipient combinations in which direct kidney transplantation is not possible. The Dutch Transplantation Foundation is responsible for the allocation, in which new donor-recipient combinations are created in accordance with four allocation criteria: blood group, match probability, time on the waiting list, and age difference between the donors. The results of the first 2 years of this programme have now been assessed. RESULTS: From January 2004 until December 2005, the national programme registered a total of 116 donor-recipient combinations, including 62 blood type incompatible pairs and 54 positive cross-match pairs. In 8 matching procedures, 58 newly created donor-recipient combinations had negative cross matches. 49 patients (42%) were transplanted. CONCLUSION: The Dutch living donor exchange programme for kidney transplantation appears to be very successful, with 42% effective transplantations in the first 2 years.

Living donor kidney exchange for both ABO-incompatible and crossmatch positive donor-recipient combinations.

BACKGROUND: Strategies to decrease the wait time for kidney transplantation include the use of living donor kidneys. However, it is not always possible to donate directly, due to ABO blood type incompatibility or a positive crossmatch. Therefore, other options were explored, including a program for living donor kidney exchange. METHODS: All Dutch kidney transplantation centers agreed on a common donor kidney exchange protocol. The Dutch Transplantation Foundation is responsible for the allocation, crossmatches are centrally performed, and exchanges take place on an anonymous basis. Donors travel to the recipient centers. Surgical procedures are simultaneously scheduled. RESULTS: From January 2004, we registered in total 116 combinations consisting of blood type-incompatible pairs (n = 62) and positive crossmatch pairs (n = 54). In eight match procedures we created 58 new donor-recipient combinations with negative crossmatches, including six triplets and 20 doublets. It proved to be significantly (P = .0014) less difficult to find a solution for the crossmatch-positive combinations than for the blood type-incompatible combinations (67% vs 35%). CONCLUSION: The Dutch national living donor kidney exchange program resulted in a 50% success rate. Combining blood type-incompatible and crossmatch-positive donor-recipient pairs in one program is a realistic option for all blood type combinations.

The Dutch donor registry: registration rate of hospital personnel, living kidney donors, and patients.

INTRODUCTION: In the Netherlands 13.3 million citizens were contacted by the Dutch donor registry to indicate whether they consented or objected to become an organ/tissue donor after death. Nearly 4.7 million individuals are now registered, which is a 35.1% response rate. We wondered whether kidney patients, living kidney donors, and health personnel would have comparable response rates. METHODS AND RESULTS: A total of 239 individuals were interviewed, of whom 52% indicated to be registered. The highest registration rate was found for hospital personnel (66%) followed by living kidney donors (51%) and patients (38%). In general, more women than men (57% vs 47%) had returned their registration form. CONCLUSION: In the Dutch general public the willingness to make their decision known during life to donate organs/tissue after death is rather low. Presumably motivated individuals (eg, hospital personnel and living kidney donors) scored significantly better, but even in these subgroups 34% and 49%, respectively, were nonresponders.

The Dutch algorithm for allocation in living donor kidney exchange.

The shortage of kidneys from brain-dead donors for transplantation has made it necessary to look for alternatives. Living kidney donation is one possibility. However, because of ABO blood group incompatibility or immunological reasons, transplantation of kidneys from a living donor is not always possible. The seven Dutch kidney transplantation centers have developed a joint protocol for crossover, or paired donor exchange, kidney transplantation. To ensure a fair chance for all participating donor-recipient pairs, the Dutch Transplantation Foundation has developed an allocation algorithm to match compatible donor-recipient pairs. A crossover match is performed every 3 months. The computer program developed by the Dutch Transplantation Foundation to match compatible donor-recipient pairs calculates the match probability (MP) of every potential recipient. The MP takes into account the peak panel-reactive antibodies (%PRA) of the recipient, the incidence within the crossover donor population of (compatible) ABO blood group, and HLA unacceptables of the recipient. The potential recipient with the lowest MP, in other words, the recipient with the smallest chance of finding a compatible donor in the pool, is ranked first. Until now, three matches have been performed in the Netherlands. A total of 53 pairs from all seven Dutch transplantation centers have participated. For 22 of the pairs a compatible donor-recipient pair was found.

Nonresident living kidney donors.

INTRODUCTION: The increasing number of immigrant residents has resulted in more foreign patients on the kidney transplant waiting list. While the willingness of their relatives to participate in a living kidney donation program is not different from that of relatives of autochthonous patients, many extra logistic and financial problems have to be solved, when the potential donor has to travel to Rotterdam. The fear of the authorities that the donor might stay in the Netherlands after donation is another hurdle. METHODS AND RESULTS: We analysed 395 living kidney transplantations performed in Rotterdam from 1981 to 2003. In 32 instances the donor came from abroad. Another 14 potential foreign donors came to Rotterdam but did not donate for various reasons. We calculated the costs for visa, travel, insurance, and loss of income. Total financial impact for the 46 (potential) donors, amounted to capital JE, Ukrainian 56,604.09, which is capital JE, Ukrainian 1768.88 per actual performed donation. One kidney donor remained illegally in the Netherlands. CONCLUSION: We conclude that the efforts and support for foreign kidney donors to come to the Netherlands is justified and cost-effective. No evidence was found for a kidney donation immigration route.

[Cross-over transplantation; a new national program for living kidney donations]. / Gepaarde donorruil; nieuw landelijk programma voor nierdonatie bij leven.

In the Netherlands, cross-over kidney transplantation has been introduced as an extra option in the living kidney donation programme. In cross-over transplantation, patients who cannot be given their own partner's kidney for immunological reasons are given a kidney from the partner of another patient in exchange for a kidney from their own partner. There is no difference in the medical indications and contraindications between direct and indirect living donation. There are no ethical obstacles since the net gain for the two couples is no different from that of direct living kidney donation and because the exchange takes place on the basis of equality. One should be aware that the extra possibilities may result in more psychological pressure on potential donors. It is important that the donation procedures start at the same moment and that the wishes of patients and donors for anonymity be preserved. A successful cross-over kidney transplantation programme requires a large pool of donors and patients. Therefore, this has been organised in a national programme. The Dutch Transplantation Foundation is responsible for the allocation of cross-over kidneys. Organ trade will thus be impossible. The seven Dutch centres for kidney transplantation have developed a protocol.

Ganglioside mimicry of Campylobacter jejuni lipopolysaccharides determines antiganglioside specificity in rabbits.

The core oligosaccharides of Campylobacter jejuni lipopolysaccharides (LPS) display molecular mimicry with gangliosides. Cross-reactive anti-LPS-antiganglioside antibodies have been implicated to show a crucial role in the pathogenesis of the Guillain-Barré and Miller Fisher syndrome. The specificity of the antiganglioside response is thought to depend on the oligosaccharide structure of the ganglioside mimic. To test this hypothesis and to investigate the potential of LPS from Campylobacter strains from enteritis patients to induce an antiganglioside response, we immunized rabbits with purified LPS from eight Campylobacter jejuni reference strains with biochemically well-defined distinct ganglioside mimics and determined the presence of antiganglioside antibodies. All rabbits produced immunoglobulin G (IgM) and IgG anti-LPS antibodies, and the specificity of the cross-reactive antiganglioside response indeed corresponded with the biochemically defined mimic. Most rabbits also had antibody reactivity against additional gangliosides, and there were slight differences in the fine specificity of the antibody response between rabbits that had been immunized with LPS from the same Campylobacter strain. High anti-LPS and antiganglioside titers persisted over a 10-month period. In conclusion, the structure of the LPS only partly determines the antiganglioside specificity. Other strain-specific as well as host-related factors influence the induction and fine-specificity of the cross-reactive anti-LPS-antiganglioside response.

Structure of Campylobacter jejuni lipopolysaccharides determines antiganglioside specificity and clinical features of Guillain-Barré and Miller Fisher patients.

Ganglioside mimicry in the lipopolysaccharide (LPS) fraction of Campylobacter jejuni isolated from Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS) patients was compared with isolates from patients with an uncomplicated enteritis. The antibody response to C. jejuni LPS and gangliosides in neuropathy patients and controls was compared as well. LPS from GBS and MFS-associated isolates more frequently contained ganglioside-like epitopes compared to control isolates. Almost all neuropathy patients showed a strong antibody response against LPS and multiple gangliosides in contrast to enteritis patients. Isolates from GBS patients more frequently had a GM1-like epitope than isolates from MFS patients. GQ1b-like epitopes were present in all MFS-associated isolates and was associated with anti-GQ1b antibody reactivity and the presence of oculomotor symptoms. These results demonstrate that the expression of ganglioside mimics is a risk factor for the development of post-Campylobacter neuropathy. This study provides additional evidence for the hypothesis that the LPS fraction determines the antiganglioside specificity and clinical features in post-Campylobacter neuropathy patients.

Guillain-Barré syndrome- and Miller Fisher syndrome-associated Campylobacter jejuni lipopolysaccharides induce anti-GM1 and anti-GQ1b Antibodies in rabbits.

Campylobacter jejuni infections are thought to induce antiganglioside antibodies in patients with Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS) by molecular mimicry between C. jejuni lipopolysaccharides (LPS) and gangliosides. We used purified LPS fractions from five Campylobacter strains to induce antiganglioside responses in rabbits. The animals that received injections with LPS from GBS-associated strains developed anti-GM1 and anti-GA1 antibodies. Animals injected with LPS from one MFS-related C. jejuni strain produced anti-GQ1b antibodies. Rabbits that were injected with Penner O:3 LPS had a strong anti-LPS response, but no antiganglioside reactivity was observed. The antiganglioside specificity in the rabbits reflected the specificity in the patients from whom the strains were isolated. In conclusion, our results indicate that an immune response against GBS- and MFS-associated C. jejuni LPS results in antiganglioside antibodies. These results provide strong support for molecular mimicry as a mechanism in the induction of antiganglioside antibodies following infections.

A case of Guillain-Barré syndrome following a family outbreak of Campylobacter jejuni enteritis.

We describe an outbreak of Campylobacter jejuni enteritis involving three family members of whom one developed Guillain-Barré syndrome (GBS). The patients' serum reacted strongly with several gangliosides and with the lipopolysaccharide (LPS) fractions from the C. jejuni strains isolated from his family members. Only low titer anti-ganglioside antibodies were found in his siblings. HLA-typing did not indicate a locus associated with auto-antibody production. Comparing the immune response in GBS patients and C. jejuni enteritis patients can be of great value in determining the additional factors that lead to post-Campylobacter GBS. Ganglioside mimicry alone is necessary but not sufficient for the induction of anti-ganglioside antibodies. Other susceptibility factors are required to induce an anti-neural immune response.

Campylobacter jejuni lipopolysaccharides from Guillain-Barré syndrome patients induce IgG anti-GM1 antibodies in rabbits.

Lipopolysaccharides (LPS) from Campylobacter jejuni strains isolated from patients with Guillain-Barré syndrome (GBS) display molecular mimicry with GM1. We immunized rabbits with C. jejuni LPS from GBS-associated strains containing a GM1-like epitope. All animals produced high titre anti-LPS antibodies that were cross-reactive with GM1. We conclude that C. jejuni strains from GBS patients are able to induce antibodies that cross-react with gangliosides and LPS. This study further confirms the role of molecular mimicry in the induction of anti-ganglioside antibodies in GBS patients.

The spectrum of antecedent infections in Guillain-Barré syndrome: a case-control study.

OBJECTIVE: To determine which antecedent infections are specifically associated with the Guillain-Barré syndrome (GBS). BACKGROUND: Infections with many agents have been reported preceding GBS. Some infections are related to specific clinical and immunologic subgroups in GBS. Most agents were reported in case reports and uncontrolled small series of GBS patients only, and their relation to GBS and its subgroups remains unclear. METHOD: A serologic study for 16 infectious agents in 154 GBS patients and 154 sex- and age-matched controls with other neurologic diseases. Acute phase, pretreatment samples were used from clinically well-defined GBS patients. The seasonal distribution of serum sampling in the GBS and control group was the same. RESULTS: Multivariate analysis showed that in GBS patients, infections with Campylobacter jejuni (32%), cytomegalovirus (13%), and Epstein-Barr virus (10%) were significantly more frequent than in controls. Mycoplasma pneumoniae infections occurred more often in GBS patients (5%) than in controls in univariate analysis. Infections with Haemophilus influenzae (1%), parainfluenza 1 virus (1%), influenza A virus (1%), influenza B virus (1%), adenovirus (1%), herpes simplex virus (1%), and varicella zoster virus (1%) were also demonstrated in GBS patients, but not more frequently than in controls. C. jejuni infections were associated with antibodies to the gangliosides GM1 and GD1b and with a severe pure motor form of GBS. Cytomegalovirus infections were associated with antibodies to the ganglioside GM2 and with severe motor sensory deficits. Other infections were not related to specific antiganglioside antibodies and neurologic patterns. CONCLUSIONS: Recent infections with C. jejuni, cytomegalovirus, Epstein-Barr virus, and M. pneumoniae are specifically related to GBS. The variety of infections may contribute to the clinical and immunologic heterogeneity of GBS.

[Estimating the future number of disabled elderly people by using a model population]. / Schatting van het toekomstige aantal hulpbehoevende ouderen met behulp van een micromodelbevolking.

PIP: "By using a model population, the composition of the future elderly population [in the Netherlands] has been simulated. Demographic forecasts and forecasts on the level of educational attainment of elderly people were used to construct this model population. As the percentage of elderly people with disabilities is expected to fall due to an increasing level of educational attainment, the number of dependent elderly people will, over the next two decades, increase much slower than the total number of elderly people." (EXCERPT)^ieng