[Intermittent fasting and human metabolic health]. / El ayuno intermitente y sus efectos en la salud metabólica en humanos.

Intermittent fasting (IF) has gained increasing scientific and general attention. Most studied forms of IF include alternate-day fasting, modified alternate-day fasting, and time-restricted eating (TRE). Several cardiometabolic effects of IF have been described in animal models and, to a lesser extent, in humans. This review analyzes the impact of IF on weight loss, glucose metabolism, blood pressure, and lipid profile in humans. A literature search was conducted in the Pubmed/Medline, Scopus, and Google Scholar databases. Controlled observational or interventional studies in humans, published between January 2000 and June 2021, were included. Studies comparing IF versus religious fasting were not included. Most studies indicate that the different types of IF have significant benefits on body composition, inducing weight loss and reducing fat mass. Changes in cardiometabolic parameters show more divergent results. In general, a decrease in fasting glucose and insulin levels is observed, together with an improved lipid profile associated with cardiovascular risk. High heterogeneity in study designs was observed, particularly in studies with TRE, small sample sizes, and short-term interventions. Current evidence shows that IF confers a range of cardiometabolic benefits in humans. Weight loss, improvement of glucose homeostasis and lipid profile, are observed in the three types of IF protocols evaluated.

PIAS2-mediated blockade of IFN-ß signaling: a basis for sporadic Parkinson disease dementia.

Familial Parkinson disease (PD) is associated with rare genetic mutations, but the etiology in most patients with sporadic (s)PD is largely unknown, and the basis for its progression to dementia (sPDD) is poorly characterized. We have identified that loss of IFNß or IFNAR1, the receptor for IFNα/ß, causes pathological and behavioral changes resembling PDD, prompting us to hypothesize that dysregulated genes in IFNß-IFNAR signaling pathway predispose one to sPD. By transcriptomic analysis, we found defective neuronal IFNß-IFNAR signaling, including particularly elevated PIAS2 associated with sPDD. With meta-analysis of GWASs, we identified sequence variants in IFNß-IFNAR-related genes in sPD patients. Furthermore, sPDD patients expressed higher levels of PIAS2 mRNA and protein in neurons. To determine its function in brain, we overexpressed PIAS2 under a neuronal promoter, alone or with human α-synuclein, in the brains of mice, which caused motor and cognitive impairments and correlated with intraneuronal phosphorylated (p)α-synuclein accumulation and dopaminergic neuron loss. Ectopic expression of neuronal PIAS2 blocked mitophagy, increased the accumulation of senescent mitochondrial and oxidative stress, as evidenced by excessive oxDJ1 and 8OHdG, by inactivating ERK1/2-P53 signaling. Conversely, PIAS2 knockdown rescued the clinicopathological manifestations of PDD in Ifnb-/- mice on restoring mitochondrial homeostasis, oxidative stress, and pERK1/2-pP53 signaling. The regulation of JAK-STAT2-PIAS2 signaling was crucial for neurite outgrowth and neuronal survival and excitability and thus might prevent cognitive impairments. Our findings provide insights into the progression of sPD and dementia and have implications for new therapeutic approaches.

Evidence of body size and shape stasis driven by selection in Patagonian lizards of the Phymaturus patagonicus clade (Squamata: Liolaemini).

During the speciation process sibling lineages accumulate differences in time (e.g. genetic, morphological, and/or ecological). Phenotypic traits such as size or shape, however, could experience rapid changes or show stasis depending on their role in survival and reproduction. The clade Phymaturus patagonicus includes 26 species characterized by a conservative morphology, and all inhabit rock crevice microhabitats in arid environments. In this study we quantify levels of morphological divergence (size and shape) among the multiple species relative to interspecific molecular divergence, and show that most species have not diverged significantly in size and/or shape to permit unambiguous species diagnosis with morphological data alone. The influence of stabilizing selection for an adaptive optimum in body size and head shape was detected for 13 of the 16 variables analyzed in an Ornstein-Uhlenbeck model. The strict dependence of these species to rock-crevice microenvironments likely explains the observed morphological stasis across the many species of the Phymaturus patagonicus group.

Molecular analysis of ancient caries.

An 84 base pair sequence of the Streptococcus mutans virulence factor, known as dextranase, has been obtained from 10 individuals from the Bronze Age to the Modern Era in Europe and from before and after the colonization in America. Modern samples show four polymorphic sites that have not been found in the ancient samples studied so far. The nucleotide and haplotype diversity of this region have increased over time, which could be reflecting the footprint of a population expansion. While this segment has apparently evolved according to neutral evolution, we have been able to detect one site that is under positive selection pressure both in present and past populations. This study is a first step to study the evolution of this microorganism, analysed using direct evidence obtained from ancient remains.

It's About Timing: Contrasting the Metabolic Effects of Early vs. Late Time-Restricted Eating in Humans.

PURPOSE OF REVIEW: Time-restricted eating (TRE), a form of intermittent fasting, restricts feeding time across the day, imposing a daily 'eating window'. The time of day when the eating window occurs could result in differential metabolic effects. Here, we describe recent intervention studies in humans assessing the metabolic consequences of an early- (i.e., eating window starting in the early morning) vs. late (i.e., eating window starting after midday)-TRE protocol. RECENT FINDINGS: Well-controlled studies indicate that both TRE protocols effectively reduce body weight and improve altered glucose metabolism, lipid profile, inflammation, or blood pressure levels. An early-TRE (e-TRE) might have a further positive impact on improving blood glucose, insulin levels, and insulin resistance. However, the studies directly assessing the metabolic consequences of an early- vs. late-TRE have shown dissimilar findings, and more well-controlled clinical trials are needed on the metabolic benefits of these two types of TRE. Evidence suggests that an e-TRE might have enhanced metabolic results, particularly regarding glucose homeostasis. More long-term studies, including larger sample sizes, are needed to assess the metabolic, circadian, and adherence benefits, together with socio-cultural acceptance of both TRE approaches.

Abdominal Compartment Syndrome (ACS) With Sigmoid Volvulus (SV): Lost Hours Are Lost Lives.

Normal intra-abdominal pressure (IAP) ranges from 0 to 5, and abdominal compartment syndrome (ACS) occurs when a sustained IAP >20 mmHg causes organ dysfunction. ACS mainly occurs in patients who are critically ill. It occurs due to an injury or disease in the abdomen or pelvic area, including trauma, abdominal surgery, acute pancreatitis, pancreatic ileus, volvulus, fecal impaction, and ruptured abdominal aortic aneurysm. If not recognized early, ACS leads to multiorgan dysfunction, shock, and sepsis and has high morbidity and mortality. Our patient was brought to the emergency department (ED) following cardiac arrest and resuscitation and was diagnosed with sigmoid volvulus (SV) and ACS. SV is seen in older men, and its presentation is often insidious and leads to bowel gangrene and ACS. The patient's delay in presenting to the hospital and the severity of his condition leads to a poor outcome despite surgery. A delay in recognizing ACS can lead to a worse outcome.

Amoxicillin-Clavulanate Induced Liver Injury in a Young Female.

Amoxicillin-clavulanate (AC) is an antibiotic widely used for various infections. It has rarely been associated with drug-induced liver injury (DILI), mainly in males 55 or older with associated alcohol consumption or medications causing liver injury. Here we present an atypical case of a 22-year-old female with a past medical history of celiac disease and alopecia areata who was prescribed AC in urgent care for bilateral cervical lymphadenopathy, nausea, and chills. Her nausea and vomiting worsened after taking AC for three days, and she developed jaundice. On workup, she was found to have deranged liver functions, and pan-lobular hepatitis was confirmed on liver biopsy. She started to improve symptomatically after withdrawing AC, and her transaminases started showing a decreasing trend.

Correction: A Case Report of Takotsubo Cardiomyopathy With Myxedema Coma.

[This corrects the article DOI: 10.7759/cureus.32652.].

Pulmonary Adenocarcinoma Mimicking Pneumonia in a Young Adult.

Lung cancer is the third most common cancer in the United States. Lung adenocarcinoma is a subtype of non-small cell lung cancer. On computed tomography (CT) it can appear as ground glass nodules, consolidative opacity, or solid mass lesions located in the periphery. Because it can appear as a consolidation, it can sometimes be confused with an infectious process such as pneumonia. We present a case of a 27-year-old male initially diagnosed with pneumonia; however, three months later, when he presented to the hospital with worsening pleuritic chest pain, fever, and dyspnea after a bronchoscopy a week before admission, pathology was positive for adenocarcinoma.

A second-generation, point-of-care immunoassay provided improved detection of Anaplasma and Ehrlichia antibodies in PCR-positive dogs naturally infected with Anaplasma or Ehrlichia species.

A validated second-generation SNAP 4Dx Plus (Idexx) incorporates new peptides for improved detection of antibodies against Anaplasma and Ehrlichia tick-borne pathogens in dogs. We compared the first- and second-generation SNAP 4Dx Plus using dogs naturally infected with Anaplasma or Ehrlichia species, or dogs seroreactive by an E. canis indirect fluorescent antibody test (IFAT). The second-generation immunoassay was more sensitive than the first-generation for dogs infected with A. phagocytophilum (51.1% and 29.2%, respectively), A. platys (63.6% and 35.3%, respectively), E. canis (96.2% and 88.3%, respectively), or E. ewingii (73.7% and 70.8%, respectively), and for dogs seroreactive by E. canis IFAT (87.3% and 83.9%, respectively). The second-generation immunoassay detected significantly more Anaplasma- or Ehrlichia-infected dogs that were Anaplasma (p < 0.001) or Ehrlichia (p = 0.031) seroreactive, respectively, than did the first-generation test. When Ehrlichia seroreactivity by E. canis IFAT and both immunoassays was compared, significantly more E. canis-infected dogs were seroreactive by E. canis IFAT than the first-generation (p = 0.006) but not the second-generation (p = 0.125) immunoassay. Significantly more E. ewingii-infected dogs were seroreactive by the first- (p = 0.011) and second-generation (p = 0.049) immunoassays than the E. canis IFAT. Medical records available for 7 dogs that were Anaplasma seroreactive by the second-generation but not the first-generation immunoassay revealed case management decisions that might have been different with an immediate anaplasmosis diagnosis, including earlier doxycycline therapy and less hospitalization. The second-generation SNAP 4Dx Plus test offered improved serologic detection of Anaplasma and Ehrlichia in naturally infected dogs.

Evaluation of Anaplasma spp. seroprevalence in dogs and association with incidence of human anaplasmosis.

Point-of-care (POC) ELISA tests are routinely used in US veterinary practices to screen canine patients for antibodies to tick-transmitted pathogens. Results are also used to monitor spatial and temporal trends in canine seroprevalence, and these data can build awareness of the risk to humans of tick-transmitted diseases such as Lyme disease and anaplasmosis. This study utilized a second-generation test that has incorporated additional Anaplasma-specific peptides into a commercial POC ELISA test to allow detection of Anaplasma spp. antibodies earlier post-infection. A convenience population consisting of 19,894 canine samples from a US commercial diagnostic laboratory were tested using the second-generation POC ELISA test to describe regional Anaplasma spp. canine seroprevalence and assess correlation to anaplasmosis cases reported to Centers for Disease Control and Prevention by state. Antibodies to Anaplasma spp. were detected in 1646 samples (8.3%) with the Northeast and Midwest US census regions having the highest proportion of positive samples. At the state level, a significant correlation was found between canine Anaplasma spp. seroprevalence and human anaplasmosis incidence (r2 = 0.64). Although estimates of canine Anaplasma spp. seroprevalence presented here using the second-generation POC ELISA are generally increased, especially in the Northeast and Midwest, the regional distribution of canine samples testing positive for Anaplasma spp. antibodies is consistent with previous reports. The observed correlation with human anaplasmosis incidence indicates that results from the second-generation POC ELISA will continue to add value in epidemiological assessment of human anaplasmosis risk.

Dexmedetomidine-Induced Fever in a 66-Year-Old Male With Pneumonia and Pleural Effusion.

Drug-induced fever is a significant adverse effect as many commonly used medications can cause this. The incidence of drug fever is even higher in critical care settings because multiple medications are being administered simultaneously. This poses a serious problem in critical care settings as any new fever in these settings also implies any new infection or worsening of preexisting conditions. This may lead to a detailed investigation for the cause of fever, which can be time-consuming, invasive, costly, and may also increase the duration of stay along with an associated increase in morbidity and mortality. We want to highlight an adverse drug event through a documented case of Dexmedetomidine-induced fever in a critical care patient with multiple pathologies.

A Case of Delayed Treatment in Cervical Spondylotic Myelopathy Presenting as Hemiplegia in an Elderly Female.

Cervical spondylotic myelopathy (CSM) is a degenerative disease of the spine that occurs mainly in the elderly, along with age-related changes in the spine. It has a varied presentation, from nonspecific paraesthesia and neck pain to hemiplegia and paraplegia, even quadriplegia, due to the compression of the cervical spine or nerves in the spinal canal or foramina. The diagnosis is often delayed, and cases may present as acute worsening and even hemiplegia mimicking stroke following trauma or neck manipulation. We present a case of CSM in an elderly female presenting with hemiplegia. There was a good recovery after surgical decompression. This case highlights the importance of a high index of suspicion and early diagnosis.

A Rare Case of Horseshoe Kidney With Multiple Atrial Myxomas Presenting as Cerebrovascular Accident.

Myxomas are benign tumors of mesenchymal origin, containing a few pluripotent cells in the myxomatous stroma. They usually present at 30-40 years of age and are more common in females than males. These tumors mostly arise in the atria and protrude into the atrial lumen. They cause constitutional symptoms like fever and weight loss and obstructive symptoms related to outflow obstruction in the heart. Some tumors are more fragile and cause embolism and may present as stroke. Mostly sporadic but familial cases and myxomas associated with Carney syndrome (CNC) tend to be multiple. Here, we report a case of a 40-year-old female with a stroke due to embolization from multiple myxomas. She had no family history of myxoma and had no skin findings or other tumors associated with CNC. She also had an atrophied horseshoe kidney with renal failure. The association of a horseshoe kidney with myxoma is rarely reported. In an extensive literature search, we could only find only one other case. Atrial myxomas were detected while investigating the cause of stroke. Our patient gradually improved and was advised surgical removal of the myxomas, which is the treatment of choice.

A Case Report of Takotsubo Cardiomyopathy With Myxedema Coma.

The exact pathogenesis of Takotsubo cardiomyopathy (TC) or broken heart syndrome is unclear. However, it is known to be a stress-induced cardiomyopathy. There are multiple causes of TC, and thyroid dysfunction is supposed to be one of the causes. We present a case of a 74-year-old female with a medical history of hypothyroidism who was admitted to the hospital with a myxedema coma and myocardial infarction. Her angiography had no evidence of plaque, thrombus, or spasm, and echocardiography showed apical ballooning, thus confirming the diagnosis of TC.

A Case Report of Sepsis Post Cardiac Catheterization.

Percutaneous coronary intervention (PCI) and cardiac catheterization are clean procedures done under aseptic precautions, but studies have shown transient bacteremia following the process, mostly involving Staphylococcus. This has many complications, from localized wounds at arterial access sites to endocarditis, mycotic aneurysm, and sepsis, and are associated with high mortality. These may require surgical intervention and prolonged antibiotic use. The risk of acquiring these infections is higher in femoral catheterization than in radial access. This risk also increases in patients with congestive cardiac failure, age 60 and above, and those with diabetes and obesity. Procedural hazards include multiple punctures and leaving the sheath for future access due to the needle tract's colonization. We present a case of sepsis presenting two days after PCI using single puncture radial access and a rapid downhill course.

An Interesting Case of Mixed Dust Pneumoconiosis With Progressive Massive Fibrosis and Cor Pulmonale in a South American Farmer.

Pneumoconiosis is an occupational disease found in workers with environmental exposure to organic and inorganic dust, as in mining, sandblasting, pottery, stone masonry, and farming. The inflammatory response of the lung to respirable dust causes the formation of macules, nodules, and fibrosis, and higher silica content in inhaled dust is associated with increased fibrosis. Mixed dust pneumoconiosis (MDP) is characterized by exposure to dust containing 10-20% silica, and its lung imaging show irregular opacities. Histopathology plays a vital role in the diagnosis of MDP. Though it has a favorable outcome, it evolves slowly over many years of constant exposure and is characterized by worsening dyspnea and cough gradually progressing to cor pulmonale. The only effective treatment is removing exposure, which makes it essential to recognize the disease early for a favorable outcome. We present a case of mixed dust pneumoconiosis in a farmer from South America who had asthma. He presented with worsening dyspnea and multiple nodules in both lungs on imaging and cor pulmonale. An extensive workup was done, and it ruled out any malignancy and tuberculosis. Analysis of video-assisted thoracoscopic surgery (VATS) biopsy samples confirmed the diagnosis of mixed dust pneumoconiosis. He had a confluence of irregular nodes in the upper lobes of the lungs, and the largest was 2.1 cm. This fits the International Labour Organization (ILO) definition of progressive massive fibrosis. This, along with cor pulmonale present in him, gives it a poor prognosis even after he is removed from dust exposure. He received steroids, which led to symptomatic improvement, and he was discharged to follow up with the pulmonologist.

An Improved Point-of-Care ELISA for the Diagnosis of Anaplasmosis and Ehrlichiosis During the Acute Phase of Tick-Borne Infections in Dogs.

Veterinarians often test for serologic evidence of vector-borne infections in sick dogs presenting with clinical signs or to screen for subclinical chronic infections. Additional peptide targets for the detection of antibodies to Anaplasma phagocytophilum, Anaplasma platys, and Ehrlichia canis were added to an existing point-of-care (POC) ELISA test (SNAP 4Dx Plus Test, IDEXX Laboratories, Westbrook, ME). This second-generation, multi-analyte test detects Dirofilaria immitis antigen and antibodies to Anaplasma spp., Borrelia burgdorferi, and Ehrlichia spp. The second-generation test is expected to better meet the needs of practicing veterinarians and their patients. To assess this expectation, the second-generation POC test was evaluated with serum samples from experimentally infected dogs and a broader field population of dogs. Compared to the first-generation test, most dogs experimentally infected with A phagocytophilum (n = 7/8), A platys (n = 4/6), or E canis (n = 4/6) had detectable antibody responses 3-22 days earlier post-infection; these results demonstrated better alignment with polymerase chain reaction (PCR) amplification results and the onset of clinical signs. Using a convenience sample set of 510 sera from both academic and commercial veterinary diagnostic laboratories, the second-generation test had sensitivities greater than 90% for Anaplasma spp. (94.1%), B burgdorferi (95.5%), Ehrlichia spp. (93.4%) and D immitis (98.0%). Specificity ranged from 96.8% - 100% across the four assays. Results from this study demonstrate that the second-generation POC ELISA had an improved ability to detect serologic responses during the acute phase of A phagocytophilum, A platys, and E canis experimental infections. The results from the broader field samples support overall high sensitivity and specificity, consistent with the historical performance of the first-generation POC ELISA test.

Assessment of dietary exposure to aflatoxin B1 from corn arepas in Colombia.

The aim of this research was to evaluate dietary exposure to aflatoxin B1 (AFB1) in corn arepas in Colombia. In addition, in this study an assessment considering compliance to the maximum level of AFB1 (4 µg kg-1) for this food was conducted. AFB1 concentration data in corn arepas were obtained from 168 samples. The samples were collected from factories in 16 departments in Colombia. AFB1 was quantified by High-Performance Liquid Chromatography with a fluorescence detector. Consumption data and body weight (b.w.) were measured from the 2005 Colombian National Survey of Nutritional Status. Probabilistic estimates were made by Monte Carlo simulation of dietary exposure and margin of exposure (MOE) segmented by age group. The results showed that 27% of corn arepa samples were contaminated with AFB1, with an average concentration of 15.1 µg kg-1 and a maximum value of 111.1 µg kg-1. The stochastic dietary exposure assessment showed that the age group most exposed was children between 4 and 8 years old (10.014 ng (kg b.w. day)-1). In addition, the MOE values for all age groups were lower than 10,000, indicating a potential risk for consumers. However, in the scenario where AFB1 concentration level complies with the maximum limit of 4 µg kg-1 AFB1, the level of concern could be reduced for the adult population between 14 and 64 years old because the MOE value is above 10,000.

MicroRNA-654-5p suppresses ovarian cancer development impacting on MYC, WNT and AKT pathways.

Ovarian cancer is the most lethal gynecological malignancy due to the silent nature on its early onset and the rapid acquisition of drug resistance. Histologically heterogeneous, it includes several subtypes with different mutational landscapes, hampering the development of effective targeted therapies. Non-coding RNAs are emerging as potential new therapeutic targets in cancer. To search for a microRNA signature related to ovarian carcinomas and study its potential as effective targeted therapy, we examined the expression of 768 miRNA in a large collection of tumor samples and found miR-654-5p to be infraexpressed in ovarian serous carcinomas, the most common and aggressive type. Restoration of miR-654-5p levels reduced tumor cell viability in vitro and in vivo and impaired sphere formation capacity and viability of ovarian cancer patient-derived ascitic cells ex vivo. CDCP1 and PLAGL2 oncogenes were found to be the most relevant direct miR-654-5p targets and both genes convey in a molecular signature associated with key cancer pathways relevant to ovarian tumorigenesis, such as MYC, WNT and AKT pathways. Together, we unveiled the tumor suppressor function of miR-654-5p, suggesting that its restoration or co-targeting of CDCP1 and PLAGL2 may be an effective therapeutic approach for ovarian cancer.