Long-term effects of different exercise training modes on cytokines and adipokines in individuals with overweight/obesity and cardiometabolic diseases: A systematic review,meta-analysis,and meta-regression of randomized controlled trials

The present study aimed to investigate the evidence on the effects of different long-term training interventions (aerobic [AeT], resistance [RT], and combined [COMB]) and spontaneous physical activity (PA) in modifying cytokines and adipokines in individuals with overweight or obesity with or without cardiometabolic diseases while considering potential confounders. Although exercise interventions have become a potentially effective tool for preventing and treating metabolic diseases, the evidence provided by previous systematic reviews is inconclusive since several potential confounders have yet to be addressed. Therefore, we conducted a systematic literature search in Medline, Cochrane, and Embase databases from January 2000 to July 2022 and performed a meta-analysis. Inclusion criteria retrieved 106 full texts comprising 8,642 individuals with a range BMI of 25.1–43.8 kg m⁻². We found that independently of the training mode, exercise had a beneficial effect on diminishing Adiponectin, C-reactive protein (CRP), IL-6, IL-18, IL-20, Leptin, sICAM, and TNF-α levels circulating levels. Furthermore, by subsequent analysis, we detected differential effects of AeT, RT, and COMB, with sex, age, body composition, and trial length acting as moderators. The comparison of training modes revealed a difference favoring COMB over AeT for regulating the increase in CRP with no differences in the remaining biomarkers. Meta-regression analysis revealed an effect of change in maximal oxygen uptake (VO_2max) on CRP, IL-6, and TNF-α, while IL-10 was influenced by the change in body fat. The results suggest that all interventions, except PA, are effective in lessening this population's inflammatory status, provided that exercise results in an increase of VO_2max.     

MAP1B binds to the NMDA receptor subunit NR3A and affects NR3A protein concentrations

Incorporation of the N-methyl-d-aspartate receptor (NMDAR) subunit NR3A into functional NMDARs results in reduced channel conductance and Ca²⁺ permeability. To further investigate the function of NR3A, we have set out to characterize its intracellular binding partners. Here, we report a novel protein interaction between NR3A and microtubule associated-protein (MAP) 1B, which both are localized to dendritic shafts and filopodia. NR3A protein levels were increased in MAP1B deficient (−/−) mice, with a corresponding decrease in NR1 levels, but the fraction of filopodia immunoreactive for NR3A was equal in cells from −/− and wild type (WT) mice. NR3A has previously been shown to interact with another member of the MAP1 family, MAP1S. We showed that MAP1S binds to microtubules in a similar manner as MAP1B, and suggest that MAP1S and MAP1B both are involved in regulating trafficking of NR3A-containing NMDAR.     

Syndromes of overdrainage of ventricular shunting in childhood hydrocephalus

Overdrainage in ventricular shunting constitutes a difficult to prevent and to treat complication. The authors reviewed a retrospective series of 512 children submitted to a ventricular shunting procedure aimed at analysing factors influencing this type of complication. The causes for the hydrocephalus were congenital (n=172), post-myelomeningocele (n=123), posthemorrhagic (n=103), tumoral (n=64), postmeningitis (n=40) and posttraumatic (n=10). Eighty-eight children (17.8%) evolved with a complication related to the excessive function of the valve. The authors investigated the relationship between hydrocephalus' etiology and type of overdrainage syndromes. The most frequent complication was ventricular catheter block (n=50), followed by symptomatic slit ventricle syndrome (SVS) (n=19), subdural hematoma (n=10) and trapped fourth ventricle (n=9). There were no statistical differences regarding complications for each etiologic subset of hydrocephalus. SVS occurred in 19 children (3.71%), a low rate according to the current literature. Posthemorrhagic and postinfectious hydrocephalus grouped together showed a higher rate of SVS (p=0.005), a feature that we attributed to the cerebral destruction caused by these two conditions. Treatment of SVS was complex and required diverse procedures, applied in an escalated way, which included five decompressive craniectomies. The authors suggest avoiding, as much as possible, the use of ventricular shunts, and recommend the alternative use of new technology valves and neuroendoscopic procedures.     

Molecular genetics of radiographically defined de novo glioblastoma multiforme

Glioblastoma multiforme (GBM) represents the final endpoint of anaplastic progression in astrocytomas. GBM which arise without clinical evidence of a prior low-grade astrocytoma (LGA) have been designated de novo GBM, and are thought to develop rapidly from initial tumour formation. However, a purely clinical definition of de novo GBM does not exclude a long-standing, asymptomatic low-grade tumour. This study therefore sought to determine the genetic features of a unique group of cases in which GBMs were documented to have arisen radiographically in defined period of time (radiographically defined de novo GBM). Clinical and genetic features were examined in a group of 11 patients with a histological diagnosis of high-grade astrocytoma at first biopsy and radiographically defined de novo GBM. The mean age of the patients at tumour diagnosis was 62 years (range 32-87). Six of 11 tumours arose in the temporal lobes. Eight of 11 tumours had epidermal growth factor receptor (EGFR) overexpression, and EGFR gene amplification was found in five of the six analysed cases. Overexpression of p53 was observed in only one tumour, and a TP53 mutation was present in this case. p16 immunostaining was undetectable in 10 cases, and homozygous deletion of CDKN2A was observed in four of the six studied tumours. pRb expression was lost in four tumours. Mutations in the PTEN gene were detected in two of six cases. The results in this unique group of cases confirms the prior hypothesis that the profile of genetic alterations in de novo GBM is distinct from that of GBM arising from a known LGA, and that these specific genetic pathways promote the rapid development of GBM.     

ANALYSIS OF HLA HAPLOTYPES IN FAMILIES WITH TYPE 1 DIABETES MELLITUS IN LA RÉUNION ISLAND

To analyse HLA and insulin-dependent diabetes mellitus (IDDM) association in the ethnically mixed population of La Réunion island, we carried out a family study on 70 diabetic subjects. HLA-DQA1, -DQB1 and -DRB1 typing was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), completed by PCR-sequence-specific oligonucleotide (SSO) and PCR-sequence-specific priming (SSP). Haplotype-relative risks (HRR) were determined with the non-transmitted parental haplotypes as controls, and relative risks (RR) were calculated with a classical case-control study. The most significant risks were found for the cis and trans combinations between DQA1*03 or *0501 (Arg52⁺) and DQB1*02 or *0302 (Asp57^?) alleles, suggesting a direct role for the HLA-DQ heterodimer in IDDM susceptibility. Interestingly, due to the mixed origin of the population, the trans-encoded DQ molecules in the (DR3)-DQA1*0501-DQB1*02/(DR4)-DQA1*03-DQB 1*0302 subjects were also found cis-encoded in patients with the (DR7 or 9)-DQA1*03-DQB1*02 haplotype and in a patient with the rare (DR 11)-DQA1*0501-DQB 1*0302 haplotype. A relative predispositional effect (RPE) analysis gave significant haplotype-IDDM⁺ associations in the following order: (DR3)-DQA1*0501-DQB1*02>(DR4)-DQA1*03-DQB1*0302>(DR9)-DQA1*03-DQB*02>(DR7)-DQA1*03-DQB1*02>(DR2)-DQA1*01-DQB1*0502. No protective effect remained significant once the susceptible haplotypes were removed. A stratification study showed a stronger influence of the DQ genes than DRB1 alleles within the DR7 haplotypes. On the other hand, IDDM subjects with only one susceptible haplotype had inherited this haplotype more often from their father than from their mother. This paternal effect could be related to the greater risk of IDDM in offspring of diabetic fathers than the risk in offspring of diabetic mothers.     

Viability and functionality of bovine chromaffin cells encapsulated into alginate-PLL microcapsules with a liquefied inner core

Implantation of adrenal medullary bovine chromaffin cells (BCC), which synthesize and secrete a combination of pain-reducing neuroactive compounds including catecholamines and opioid peptides, has been proposed for the treatment of intractable cancer pain. Macro- or microencapsulation of such cells within semipermeable membranes is expected to protect the transplant from the host's immune system. In the present study, we report the viability and functionality of BCC encapsulated into microcapsules of alginate-poly-L-lysine (PLL) with a liquefied inner core. The experiment was carried out during 44 days. Empty microcapsules were characterized in terms of morphology, permeability, and mechanical resistance. At the same time, the viability and functionality of both encapsulated and nonencapsulated BCC were evaluated in vitro. We obtained viable BCC with excellent functionality: immunocytochemical analysis revealed robust survival of chromaffin cells 30 days after isolation and microencapsulation. HPLC assay showed that encapsulated BCC released catecholamines basally during the time course study. Taken together, these results demonstrate that viable BCC can be successfully encapsulated into alginate-PLL microcapsules with a liquefied inner core.     

Poor correlation between delayed neuronal death induced by transient forebrain ischemia,and immunoreactivity for parvalbumin and calbindin D-28k in developing gerbil hippocampus

In the normal developing hippocampus of the gerbil, parvalbumin-immunoreactive neurons first appear in the stratum pyramidale of CA3 at postnatal day 15 (P15), and in CA2 and hilus of the dentate gyrus from P21 onwards. Immunoreactive terminals also follow the same sequence from CA3 to CA1 to reach adult patterns by the end of the 1st month. Calbindin D-28k immunoreactivity is seen in the external part of the upper blade of the dentate gyrus at P5, and progresses to the granule cell and molecular layers of the whole gyrus by P15, except for a thin band of immature cells located at the base of the granule cell layer which are calbindin negative. Calbindin immunoreactivity in mossy fibers progresses from the external to the hilar region of CA3 during the same period. A few immunoreactive cells are also found in the stratum radiatum/lacunare of the CA3, but no calbindin-immunoreactive cells are observed in the CA1 and CA2 subfields. The adult pattern of calbindin immunoreactivity is reached at P21. Vulnerability following transient forebrain ischemia for 20 min was examined in the hippocampal formation of gerbils during postnatal development. No cellular damage was seen in animals aged 7 days. Dying cells were observed at the base of the granule cell layer of the dentate gyrus in animals aged 15, 21 and 30 days. Pyramidal cells in the CA3 subfield were also sensitive to ischemia in gerbils aged 15 days, and less frequently in animals aged 21 days. The adult pattern of cellular damage, characterized by selective vulnerability of the CA1 subfield, was seen from day 30 onwards. These findings show that the pattern of selective vulnerability following transient forebrain ischemia is different in young and adult gerbils, and suggest that little, if any, correlation exists between resistance to delayed cellular damage and parvalbumin and calbindin D-28k content in the hippocampus of young gerbils.Supported in part by grant FIS 93-131 and a grant from the Fundacio Pi i Synyer (to A.T.)