Intermediary Condition Research Articles

Muscle Fiber Heterogeneity of Insulin Sensitivity in Syntaxin-4 Enriched Skeletal Muscle

Skeletal muscle insulin resistance (IR) is a primary cause for prediabetes, an intermediary condition of higher-than-normal blood glucose levels that left untreated progresses into type 2 diabetes (T2D). A number of contributing factors associated with skeletal muscle IR include aberrant mitochondrial function, elevated reactive oxygen species, inflammation, and reduction in oxidative slow-twitch type 1 skeletal muscle fibers. One leading candidate for reversing skeletal muscle IR is Syntaxin 4 (STX4), traditionally a cell surface transmembrane SNARE protein for GLUT4 vesicle exocytosis that our lab has recently discovered is also localized in the skeletal muscle outer mitochondrial membrane. Importantly, we previously demonstrated that doxycycline-induced skeletal muscle specific STX4 overexpression in obese, prediabetes male transgenic mice (skmSTX4-iOE) reversed IR and mitochondrial dysfunction associated with diabetes muscle. However, the precise mechanisms of how STX4 restores skeletal muscle insulin sensitivity remains to be determined. To test glucose uptake and insulin sensitivity we used the “gold standard” method of hyper-insulinemic-euglycemic clamp in chow-fed skmSTX4-iOE STX4 enriched mice against non-induced controls, we identified improved glucose clearance was only associated with increased insulin sensitivity in type 1 fiber rich soleus muscle. On the other hand, insulin tolerance test studies in doxycycline-induced skeletal muscle STX4 knockout (skmSTX4-iKO) male mice revealed the opposite phenotype, suggesting that STX4 activity in slow-twitch skeletal muscle may be a contributing factor for the reversal of IR. To determine the heterogeneity of STX4 activity between different skeletal muscle fibers, myogenic precursors and intercalating non-muscular tissue in skeletal muscle STX4 enriched skmSTX4-iOE mice, we aim to use our established single nuclear RNA-Sequencing platform (snRNA-Seq) to identify pathways in distinct fiber types associated with STX4 enrichment. Overall, our work aims to determine the functional requirements of STX4 in slow-and-fast twitch skeletal muscle fiber types and identify novel molecular pathways that may serve as useful targets for the reversal/protection against skeletal muscle IR in prediabetes and T2D. This study was supported by grants from the National Institutes of Health (DK067912, DK1129712 and DK102233) and City of Hope Shared Resources Pilot Grant. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Safety and efficacy of acupuncture for mild cognitive impairment: a study protocol for clinical study.

Mild cognitive impairment (MCI) is an intermediary condition between typical cognitive decline that occurs owing to aging and dementia. It is necessary to implement an intervention to slow the progression from MCI to Alzheimer's disease. This manuscript reports the protocol for a clinical trial on the effect of acupuncture in patients with MCI. The trial will be a randomized, prospective, parallel-arm, active-controlled trial. Sixty-four patients with MCI will be randomized to the Rehacom or acupuncture group (n = 32 each). The participants in the acupuncture group will receive electroacupuncture at GV24 (Shenting) and GV20 (Baihui) and acupuncture at EX-HN1 (Sishencong) once (30 min) a day, twice per week for 12 weeks. The patients in the Rehacom group will receive computerized cognitive rehabilitation using RehaCom software once (30 min) daily, twice weekly for 12 weeks. The primary outcome measure is the change in the Montreal Cognitive Assessment Scale score. The secondary outcome measures are the Geriatric Depression Scale, Alzheimer's Disease Assessment Scale-Korean version-cognitive subscale-3 scores, and European Quality of Life Five Dimensions Five Level Scale. The safety outcomes will include the incidence of adverse events, blood pressure, blood chemistry parameters, and pulse rate. The efficacy outcome will be assessed at baseline and at six weeks, 13 weeks, and 24 weeks after baseline. The findings of this protocol will provide information regarding the effects of acupuncture on MCI. https://cris.nih.go.kr/cris/search/detailSearch.do?search_lang=E&focus=reset_12&search_page=M&pageSize=10&page=undefined&seq=25579&status=5&seq_group=25579, KCT0008861.

Recurrent febrile seizures alter intrahippocampal temporal coordination but do not cause spatial learning impairments.

Febrile seizures (FSs) are the most common form of seizures in children. Single short FSs are benign, but FSs lasting longer than 30min, termed febrile status epilepticus, may result in neurological sequelae. However, there is little information about an intermediary condition, brief recurrent FSs (RFSs). The goal of this study was to determine the role of RFSs on spatial learning and memory and the properties of spontaneous hippocampal signals. A hippocampus-dependent active avoidance task was used to assess spatial learning and memory in adult rats that underwent experimental RFSs (eRFSs) in early life compared with their littermate controls. Following completion of the task, we utilized high-density laminar probes to measure spontaneous hippocampal CA1 circuit activity under urethane anesthesia, which allowed for the simultaneous recording of input regions in CA1 associated with both CA3 and entorhinal cortex. RFSs did not result in deficits in the active avoidance spatial test, a hippocampus-dependent test of spatial learning and memory. However, in vivo high-density laminar electrode recordings from eRFS rats had significantly altered power and frequency expression of theta and gamma bandwidths as well as signaling efficacy along the CA1somatodendritic axis. Thus, although eRFS modified CA1 neuronal input/output dynamics, these alterations were not sufficient to impair active avoidance spatial behavior. These findings indicate that although eRFSs do not result in spatial cognitive deficits in the active avoidance task, recurrent seizures do alter the brain and result in longstanding changes in the temporal organization of the hippocampus.

Seasonal and event-driven changes in the phytoplankton communities in the Araçá Bay and adjacent waters

Biomass and composition of phytoplankton are reported for the Araçá Bay (AB) and adjacent waters in the São Sebastião Channel (SSC) in relation to physical-chemical variables. The AB has unequivocal ecological and socio-economic importance but it is under current anthropic pressures that are expected to increase. Needed future management programs require establishing the natural scales of variability of the phytoplankton communities and main drivers. In this study, samplings were conducted every 5–6 weeks from September 2013 to August 2014 to evaluate the extent to which AB and SSC differ in time. The approach was: 1) to compare nutrient concentration and phytoplankton abundance and composition found at AB and adjacent SSC waters; 2) to associate significant changes in nutrient concentration and in phytoplankton composition with time and main meteo-oceanographic processes, such as changes in wind direction or intrusions of upwelled South Atlantic Central Water (SACW). Sampling design included two parallel sections of oceanographic stations (inside and outside AB) that were repeated in the morning and afternoon for 3 consecutive days. Temperature, salinity and chlorophyll-a fluorescence were measured vertically, and discrete water samples were collected for analyses of inorganic nutrients, chlorophyll (Chla) and enumeration of selected groups of phytoplankton. SSC water masses characteristics showed clear seasonality but also a significant hourly to daily variability driven by changes in wind speed and direction. Nutrients and Chla varied mainly on a scale of days, as did phytoplankton abundances and compositions and all variables compared were consistently higher at AB. Samplings were characterized in four groups: 1) warm and stratified waters, 2) cold and homogenous waters, 3) low salinity waters, and 4) an intermediary condition between groups 1 and 3. Diatoms were numerically important, including the potential bloom forming Pseudo-nitzschia spp, which were more frequent during warm and stratified conditions, when SACW intrusions were observed. Occurrences of Asterionellopsis spp and Trichodesmium spp were associated with changes in wind direction. Future monitoring programs in the region should combine short-time coastal observations and near-real-time regional hydrodynamic models. The results raise the awareness for the increasing urban expansion, inefficient sewage treatment and changes in the hydrodynamics of AB.

Environmental enteropathy.

Environmental enteropathy has long been recognized as an important intermediary condition leading to chronic malnutrition in children in developing countries. Interest has lately renewed in this topic because of increased focus on improving the quality of lives as opposed to just saving them. Here, we provide an overview of recent scientific literature and our perspective about this disorder. Current understanding of the disorder of environmental enteropathy is based on studies conducted decades ago. Results of some new studies on histopathologic characterization of environmental enteropathy are currently awaited. Given the challenges of diagnosing environmental enteropathy using the gold standard test of intestinal biopsy, different biomarkers have been tested as proxies of environmental enteropathy and eventually, chronic malnutrition. Available data fail to point toward a single ideal biomarker, though considerable work is still ongoing. A few interventional studies have also been conducted with improvement in environmental enteropathy as outcome. The basic histopathology of environmental enteropathy has been defined previously, and more advanced analysis to study the pathophysiology of this disorder is currently being carried out. Many biomarkers, which represent the different mechanisms involved in environmental enteropathy, have been tested as proxies of environmental enteropathy. Although no single biomarker fits the description of an ideal biomarker yet, a few of the more promising biomarkers are being validated in different studies. Finally, the few interventions which have been tried to treat environmental enteropathy, thus far, are summarized.

Metabolic Burden and Disease and Mortality Risk Associated with Impaired Fasting Glucose in Elderly Adults.

To examine whether impaired fasting glucose (IFG) represents an intermediary condition between normal fasting glucose and diabetes mellitus and, specifically, whether elderly adults with IFG have higher disease burden, cardiovascular risk, and systemic inflammation and higher 2-year mortality and incident disease. Prospective observational study. Population-derived cohort. Individuals with a mean age of 78.6 ± 4.7 (N = 945). Disease was ascertained using a standardized questionnaire at baseline and 2 years. Fasting metabolic, inflammatory, and oxidative metabolism markers were measured. Disease prevalence, cardiovascular risk, and biochemical markers were compared to determine disease burden and metabolic disturbances in IFG. Adjusted odds ratios (ORs) for 2-year all-cause mortality and incident disease were determined. IFG prevalence was 41%. Individuals with IFG had higher baseline rates of heart disease than those with normal fasting glucose (NFG), similar to that in individuals with diabetes mellitus. IFG was characterized by higher inflammatory markers and oxidative metabolism end products and was an intermediary between NFG and diabetes mellitus for triglycerides and malondialdehyde. Discriminant analysis showed that IFG was independently associated with stroke and higher triglycerides and oxidative stress. Two-year all-cause mortality was 3.9%. The 2-year adjusted ORs for all-cause mortality, incident cardiac disease, stroke, and cancer were similar between IFG and NFG, using both American Diabetes Association and World Health Organization IFG criteria. IFG did not predict secondary cardiac events, stroke, or cancer. IFG was an intermediary condition for heart disease, inflammation, and oxidative stress in elderly adults but not for 2-year incident disease or all-cause mortality. Longer-term prospective studies are needed to clarify whether IFG in elderly adults portends greater morbidity and mortality.

Generation gland morphology in cordylid lizards: An evolutionary perspective

To elucidate the functional significance of the three distinct types of generation glands that have been identified among cordylid lizards, we mapped gland type to the terminal taxa in the most recent phylogenetic tree for the Cordylidae. We used the phylogenetic programme Mesquite and applied the principle of parsimony to infer character states for the ancestral nodes in the tree. For those species where information on gland type was not available from the literature, we conducted a histological investigation of generation gland morphology, using standard histological techniques. We included two species of the sister family Gerrhosauridae in the analysis to serve as outgroups. In both Gerrhosaurus typicus and G. flavigularis, scales immediately anterior to the femoral pores displayed glandular activity, but differed from generation glands of cordylids in the absence of mature glandular generations. Among the cordylids investigated, we identified a fourth type of generation gland in Pseudocordylus subviridis, P. spinosus, and in the two Hemicordylus species, one where the glands consistently comprise of two mature glandular generations. In H. capensis, both single- and two-layer type glands are present. Our reconstruction of ancestral character states suggests a minimum of six transformations from one gland type to another during the evolutionary history of the family. The reconstruction furthermore suggests that the single-layer type gland reappeared at least once (in Hemicordylus) in the Cordylinae after having been lost. The reconstruction also unequivocally shows that the pit-like multiple-layer type gland evolved directly from the single-layer type and not from the protruding multiple-layer type. The two-layer type gland appears to be an intermediary condition between the multiple-layer and single-layer types. The evolutionary transformation of generation gland type appears to be linked to changes in lifestyle and associated changes in degree of territoriality and the need for chemical communication.

Succession of fish and crustacean assemblages following reinstatement of tidal flow in a temperate coastal wetland

Fish and decapod crustacean assemblages were sampled from two manipulated creeks in which tidal flow had been increased through culvert removal. Assemblages were compared to those of two control creeks where culverts remained and two reference creeks without culverts. The presence of culverts reduced the richness and abundance of estuarine–marine dwelling species. Successional changes over a 16 year period (2 years prior to culvert removal and 14 years after) showed an immediate response at one manipulated creek but many years to attain reference condition. The other manipulated creek showed a completely different trajectory: oscillation between control and reference status with no clear intermediary condition. We concur with other investigators that short-term studies may give only a partial indication of response to rehabilitation efforts in coastal wetlands and longer-term studies (5–10 years) are recommended. There is some evidence that over longer-time frames, the presence of distinct groups of fish and/or decapods may indicate stages in the maturation of a rehabilitated wetland.

Do Research Intermediaries Reduce Perceived Coercion to Enter Research Trials Among Criminally Involved Substance Abusers?

We examined the efficacy of including a research intermediary (RI) during the consent process in reducing participants' perceptions of coercion to enroll in a research study. Eighty-four drug court clients being recruited into an ongoing study were randomized to receive a standard informed consent process alone (standard condition) or with an RI (intermediary condition). Before obtaining consent, RIs met with clients individually to discuss remaining concerns. Findings provided preliminary evidence that RIs reduced client perceptions that their participation might influence how clinical and judicial staff view them. This suggests that using RIs may improve participant autonomy in clinical studies.

Review article: Managing sleep apnoea in kidney diseases

A higher prevalence of sleep apnoea (SA) has been observed in the chronic kidney disease (CKD) population compared with estimates in the general population. Increased rates of SA have been described in patients with various renal-related diagnoses including dialysis, renal transplant, early-stage CKD and proteinuria. The mechanism or underlying aetiology for this association is different for each type of kidney disease. The extracellular fluid volume and metabolic derangements that characterize the uremic state likely contributes to SA in the dialysis population. SA causing direct renal insults from haemodynamic changes, ischaemic stress, or an intermediary condition such as hypertension, can lead to early CKD and proteinuria. While renal transplantation has cured SA in some patients, the post-transplant state is itself a risk factor for SA. The high prevalence of SA in kidney disease and the associated clinical implications warrant vigilance in diagnosis and treatment of SA in the CKD patient. This review focuses on the prevalence of SA in patients with CKD including dialysis and transplant patients, and those with early-stage CKD and proteinuria. SA may vary in form and aetiology depending on type or stage of CKD. Based on these associations, we discuss our rationale for recommendations on screening and management of SA specific to the CKD population.

VENTILATOR-ASSOCIATED TRACHEOBRONCHITIS IN A MIXED SURGICAL AND MEDICAL INTENSIVE CARE UNIT POPULATION

PURPOSE: Ventilator-associated tracheobronchits (VAT) has received attention as an intermediary condition between colonization of the upper respiratory tract and ventilator-associated pneumonia (VAP). Antibiotic therapy for VAT has been touted as a method of preventing subsequent VAP. However, little is known about the incidence of VAT or outcomes associated with it. This study aims to calculate the incidence of VAT relative to VAP in a mixed medical and surgical intensive care unit (ICU) population. In addition, etiologic pathogens and clinical outcomes associated with VAT will be determined.

A new species of Trachycephalus (Amphibia, Anura, Hylidae) from the State of Goiás, Brazil

A new species of Trachycephalus is described for the Cerrado biome of Goiás, Brazil. Trachycephalus mambaiensis sp. nov. is distinguished from the other ten species of the genus by the skin co-ossified with the skull, heavy cranial ossification, frontoparietal that fails to articulate with squamosal, absence of a crista occipitalis and secreting glands of milky and viscous substances. The skull of the new species shows an intermediary condition between species of Trachycephalus with a well ossified skull (Casque-headed frogs) and those without cranial ossification.

Comparative study of carotenoids from two parasitic isopoda, Urobopyrus processae and Pliophryxus philonika with those from their host, Processa edulis (crustacea, caridea)

1. 1. The carotenoids of the prawn P. edulis and two of its parasites, the Epicarids Urobopyrus processae and Pliophryxus philonika have been compared. 2. 2. The prawn contains more pigment (95.6 μg/g) than its parasites (17.6 and 13.4 μg/g respectively). 3. 3. Carotenoids are mostly in the chromatophores of the prawn, but they are in the ovary and eggs of the parasites. 4. 4. Pigment composition is different in the three species: astaxanthin esters and astaxanthin are dominant in P. edulis, β-carotene is the main pigment in U. processae, while an intermediary condition is found in P. philonika.