Aperiodic neural activity is a biomarker for depression severity.

A reliable physiological biomarker for Major Depressive Disorder (MDD) is necessary to improve treatment success rates by shoring up variability in outcome measures. In this study, we establish a passive biomarker that tracks with changes in mood on the order of minutes to hours. We record from intracranial electrodes implanted deep in the brain - a surgical setting providing exquisite temporal and spatial sensitivity to detect this relationship in a difficult-to-measure brain area, the ventromedial prefrontal cortex (VMPFC). The aperiodic slope of the power spectral density captures the balance of activity across all frequency bands and is construed as a putative proxy for excitatory/inhibitory balance in the brain. This study demonstrates how shifts in aperiodic slope correlate with depression severity in a clinical trial of deep brain stimulation for treatment-resistant depression (TRD). The correlation between depression severity scores and aperiodic slope is significant in N=5 subjects, indicating that flatter (less negative) slopes correspond to reduced depression severity, especially in the ventromedial prefrontal cortex. This biomarker offers a new way to track patient response to MDD treatment, facilitating individualized therapies in both intracranial and non-invasive monitoring scenarios.

Default mode network spatio-temporal electrophysiological signature and causal role in creativity.

The default mode network (DMN) is a widely distributed, intrinsic brain network thought to play a crucial role in internally-directed cognition. It subserves self-referential thinking, recollection of the past, mind wandering, and creativity. Knowledge about the electrophysiology underlying DMN activity is scarce, due to the difficulty to simultaneously record from multiple distant cortical areas with commonly-used techniques. The present study employs stereo-electroencephalography depth electrodes in 13 human patients undergoing monitoring for epilepsy, obtaining high spatiotemporal resolution neural recordings across multiple canonical DMN regions. Our results offer a rare insight into the temporal evolution and spatial origin of theta (4-8Hz) and gamma signals (30-70Hz) during two DMN-associated higher cognitive functions: mind-wandering and alternate uses. During the performance of these tasks, DMN activity is defined by a specific pattern of decreased theta coupled with increased gamma power. Critically, creativity and mind wandering engage the DMN with different dynamics: creativity recruits the DMN strongly during the covert search of ideas, while mind wandering displays the strongest modulation of DMN during the later recall of the train of thoughts. Theta band power modulations, predominantly occurring during mind wandering, do not show a predominant spatial origin within the DMN. In contrast, gamma power effects were similar for mind wandering and creativity and more strongly associated to lateral temporal nodes. Interfering with DMN activity through direct cortical stimulation within several DMN nodes caused a decrease in creativity, specifically reducing the originality of the alternate uses, without affecting creative fluency or mind wandering. These results suggest that DMN activity is flexibly modulated as a function of specific cognitive processes and supports its causal role in creative thinking. Our findings shed light on the neural constructs supporting creative cognition and provide causal evidence for the role of DMN in the generation of original connections among concepts.

Are there ways to improve the citations of a scientific paper?

BACKGROUND: The expansion of scientific publications makes more difficult the mining of relevant information necessary for a productive appraisal of authors' work, scientific interaction and exchange. Papers over-citation is unproductive, under-citation of innovative research generates delay and inefficiency. The extraction of information from the literature is mostly based on keywords (KWs). METHODS: I computed the chances of citation of one paper as 1/number of papers retrieved by the KWs published in that paper, and compared them with the chances obtained by selecting different KWs. RESULTS: Using generic KWs the chances are smaller, at times practically nil, as compared to those calculated with more specific KWs and their association. CONCLUSIONS: Selecting scientifically-analyzed KWs, specific for the message conveyed by a paper and computing beforehand the theoretical chances of citation, might increase the citations obtained, the retrieval of important scientific and innovative information, optimize scientific exchange and qualitative productivity. LEARNING POINTS.

Distinct brain signatures of content and structure violation during action observation.

Sentences, musical phrases and goal-directed actions are composed of elements that are linked by specific rules to form meaningful outcomes. In goal-directed actions including a non-canonical element or scrambling the order of the elements alters the action's content and structure, respectively. In the present study we investigated event-related potentials of the electroencephalographic (EEG) activity recorded during observation of both alterations of the action content (obtained by violating the semantic components of an action, e.g. making coffee with cola) and alterations of the action structure (obtained by inverting the order of two temporally adjacent pictures of sequences depicting daily life actions) interfering with the normal flow of the motor acts that compose an action. Action content alterations elicited a bilateral posterior distributed EEG negativity, peaking at around 400 ms after stimulus onset similar to the ERPs evoked by semantic violations in language studies. Alteration of the action structure elicited an early left anterior negativity followed by a late left anterior positivity, which closely resembles the ERP pattern found in language syntax violation studies. Our results suggest a functional dissociation between the processing of action content and structure, reminiscent of a similar dissociation found in the language or music domains. Importantly, this study provides further support to the hypothesis that some basic mechanisms, such as the rule-based structuring of sequential events, are shared between different cognitive domains.

Listening to speech recruits specific tongue motor synergies as revealed by transcranial magnetic stimulation and tissue-Doppler ultrasound imaging.

The activation of listener's motor system during speech processing was first demonstrated by the enhancement of electromyographic tongue potentials as evoked by single-pulse transcranial magnetic stimulation (TMS) over tongue motor cortex. This technique is, however, technically challenging and enables only a rather coarse measurement of this motor mirroring. Here, we applied TMS to listeners' tongue motor area in association with ultrasound tissue Doppler imaging to describe fine-grained tongue kinematic synergies evoked by passive listening to speech. Subjects listened to syllables requiring different patterns of dorso-ventral and antero-posterior movements (/ki/, /ko/, /ti/, /to/). Results show that passive listening to speech sounds evokes a pattern of motor synergies mirroring those occurring during speech production. Moreover, mirror motor synergies were more evident in those subjects showing good performances in discriminating speech in noise demonstrating a role of the speech-related mirror system in feed-forward processing the speaker's ongoing motor plan.

Toxocara encephalitis presenting with autonomous nervous system involvement.

Human toxocariasis has been reported to cause a broad spectrum of neurological syndromes, including encephalitis, meningitis and meningo-radiculitis. Nevertheless, cerebral infection by Toxocara may go undiagnosed due to its rarity, elusive symptoms and lack of availability of appropriate testing. We report the case of a 54-year-old man who presented with abdominal pain and paralytic ileus approximately 3 weeks after having eaten raw snails (a folk remedy for peptic ulcer). Three weeks later, marked eosinophilia ensued, associated with mental clouding, nystagmus, diplopia, peripheral limbs ataxia, urinary retention, slackened deep tendon reflexes, arthralgias and myalgias. Cerebrospinal fluid (CSF) examination demonstrated an eosinophilic meningitis, and Toxocara canis cerebral infection was diagnosed by positive serology and by the detection of T. canis DNA in the CSF. The patient made a full recovery following treatment with albendazole and corticosteroids. Physicians should be aware of this rare presentation of toxocariasis, whose diagnosis is, today, facilitated by molecular biology techniques. A history of ingestion of raw snails may alert the clinician to consider the possibility of such an uncommon condition.

The management of type 2 diabetic patients with hypoglycemic agents.

Aims and Scope. Aims of the paper are to suggest the best treatment to improve the glycemic control in patients with Type 2 diabetes using hypoglycemic agents, in particularly, we think that every patient is different from another one in terms of BMI, family history, duration of the disease and so on. We propose for every clinical aspect the best hypoglycemic agents to use, considering the scientific evidence and physiopathology.

Assessing water-electrolyte changes of hyperglycaemic hyperosmolar coma.

AIM: We reported new methods to accurately estimate salt and water deficits during hyperglycaemic hyperosmolar coma (HC), valid under restricted boundary conditions. The accuracy of these estimates is herein verified over the unrestricted spectrum of abnormalities, to correctly evaluate any patient with just one algorithm that recognizes the boundary conditions pertaining to each abnormality, choosing the appropriate calculations. METHODS: A large number of cases of HC was simulated on computer by subtracting an exhaustive combination of water, sodium and chloride losses coupled to a large variety of gains in glucose. Altered solute concentrations were generated. From these true plasma concentrations generated by the computer, the losses of water and electrolytes were back-calculated with our new computational algorithm, by knowing in addition only the normal total body water and extra-cellular volume. The accuracy of the method was tested by comparing true to calculated values over the entire range of deranged values. In 100 patients admitted to hospital for HC these same computations were performed, where calculated data were validated by comparing them to true data obtained by balance studies performed during correction of the abnormality. RESULTS: Both in simulated and real cases of HC true and calculated data for the changes in Na and volume were significantly correlated (R (2)=0.76 and 0.50, respectively, P<0.01), while their mean values were not significantly different by paired "t" tests (P>0.05 for all). CONCLUSION: Our new computation algorithm, applicable to the bed-side, useful in accurately assessing the average water-electrolyte deficits of HC, can be used to guide correct re-infusion strategies.

Is there a place for pigtail drains in the management of gastric leaks after laparoscopic sleeve gastrectomy?

Laparoscopic sleeve gastrectomy (LSG) has a specific morbidity profile in which gastric leak (GL) is the main complication. With a view to defining a standardized protocol for GL management, the present retrospective study sought to describe the clinical patterns of post-LSG GL and treatment of the latter in our university medical center. From July 2004 to December 2010, 25 patients were included. GL was described in terms of clinical presentation, time to onset, and location in the staple line. Treatment of GL with pharmacologic, radiologic, endoscopic, and/or surgical procedures was always validated by a multidisciplinary care team. "Treatment success" was defined as the absence of contrast agent leakage on CT and endoscopy after removal of covered metallic stent or pigtail drains. Systemic inflammation and peritonitis were the main signs for early-onset GL (56%), whereas pulmonary symptoms and intra-abdominal abscesses revealed delayed-onset GL (44%). Surgery was always performed for early-onset GL. In the total study population, the median number of endoscopic procedures was five (range, 1-11) per patient, of covered SEMS was three (range, 1-8), and of pigtail drains was three (range, 1-4). Nine (36%) patients presented endoscopic-related complications. Four (16%) patients with treatment failure underwent radical surgery. The mortality rate was 4% (n = 1). The management of post-LSG GL is challenging. Surgery was always performed for early-onset GL, whereas treatment of delayed-onset GL was based on endoscopy. Pigtail drains required fewer procedures per patient, were better tolerated, and had lower morbidity-mortality than covered SEMS.

Expanding the clinical use of standard OGTT: the percentage increment of 2 h with respect to fasting glucose as an index of ß-cell dysfunction.

AIMS: Since glucose levels during oral glucose tolerance test (OGTT) are determined both by insulin sensitivity and insulin secretion, we investigated whether the percentage increment (PG%) of 2-h plasma glucose (2hPG) over fasting plasma glucose (FPG) is related to validated indexes of insulin sensitivity and insulin secretion. METHODS: Using Stumvoll's formulas we calculated estimated insulin sensitivity index and first-phase insulin secretion in 1281 subjects who underwent a standard OGTT. The ratio first-phase insulin secretion/(1/estimated insulin sensitivity index) was considered a surrogate index of ß-cell function. For each subject we calculated PG% using the formula: [(2hPG - FPG)/FPG] × 100. For each glucose tolerance group we formed tertiles based on PG% values. RESULTS: In each glucose tolerance group, ß-cell function was better preserved in lower PG% tertiles, demonstrating a correlation between PG% and insulin resistance. CONCLUSIONS: By a simple calculation, our study allows, expansion of the clinical use of OGTT to recognize subjects liable to further worsening of glucose homeostasis, independent from glucose tolerance groupings.

The oral glucose tolerance test (OGTT) revisited.

The oral glucose tolerance test (OGTT) has been the mainstay for diagnosing diabetes for decades. Recently, the American Diabetes Association (ADA) suggested abandoning the OGTT, while resorting to a simpler screening test, exclusively based on baseline fasting blood glucose concentration. This review article rewinds the history of OGTT and its recent advancements, and compares its power in detecting early diabetes with that of fasting blood glucose alone. The key point is that there are more diabetics originating from a population with normal fasting blood glucose than from subjects with impaired fasting glucose, those who can be detected by the new ADA recommendations. Conversely, the OGTT detects more efficiently early diabetes as well as subjects with IGT, as the glycemia at the second hour seems crucial as a diagnostic tool. We discuss the different significance of fasting versus second hour glycemia during OGTT, according to different mechanisms of glucose homeostasis. Finally, we provide recent evidence on very simple additional information that can be obtained from the OGTT, which renders this test even more useful, discussing pathophysiologic significance.

ApoB/apoA-I ratio is better than LDL-C in detecting cardiovascular risk.

BACKGROUND AND AIMS: Cardiovascular (CV) events occur even when LDL-C are <100mg/dL. To improve the detection of CV risk we investigated the apoB/apoA-I ratio versus LDL-C in subjects considered normal glucose tolerant (NGT) by oral glucose tolerance test (OGTT). METHODS AND RESULTS: We enrolled 616 NGT (273 men and 343 women), and we measured insulin resistance, lipid profile, apoB/apoA-I and the factors compounding the metabolic syndrome (MetS). An unfavourable apoB/apoA-I (≥0.9 for males and ≥0.8 for females) was present in 13.9% of 108 patients with LDL-C <100mg/dL: compared to subjects with lower apoB/apoA-I (<0.9 for males and <0.8 for females), they had more elements of MetS and their lipid profile strongly correlated with high CV risk. Out of 314 patients with lower apoB/apoA-I, 40.12% had LDL-C ≥130mg/dL: these retained a more favourable lipid profile than corresponding subjects with elevated apoB/apoA-I ratio. Finally, we found a significant correlation between LDL-C and apoB/apoA-I ratio (r=0.48, p<0.0001). CONCLUSIONS: In NGT with LDL-C <100mg/dL, a higher apoB/apoA-I exhibited an atherogenic lipid profile, indicating that LDL-C alone is insufficient to define CV risk. Independent from LDL-level, when apoB/apoA-I is lower, the lipid profile is, in fact, less atherogenic. This study demonstrates that apoB/apoA-I is at least complementary to LDL-C in identifying the "effective" CV risk profile of asymptomatic NGT subjects.

Computation of Na and water deficit of iso-osmolar dehydration.

BACKGROUND AND AIMS: The presence of altered plasma Na concentration (PNa) allows calculations of changes in water and electrolyte contents, which are not feasible during normonatremic derangements. We have developed a computational algorithm whereby the changes in solute (ΔNa and ΔCl) and solvent (ΔV) contents can be computed exactly when Na is lost entirely as NaCl (or NaHCO(3)) and nearly exactly in all other circumstances, except when the losses of Na and Cl occur in the same proportions as those of the normal plasma concentration of these ions. METHODS: In computer experiments, we simulated different fluid depletions containing 140 mEq/l of Na (which is to say, ΔNa/ΔV ≈ 140), coupled with variable ratios in Na to Cl losses (variable ΔNa/ΔCl). The data were back-calculated with our algorithms from the ensuing plasma ion concentrations (PNa(1), PCl(1) and POAN(1), where subscript (0) and (1) indicate normal and deranged plasma concentration values, respectively, and OAN indicates anions other than Cl), as if they had been measured on patients, and from known normal values (TBW(0), ECV(0), Na(0)). These were compared to the true values used to build the simulations. This procedure was reproduced in 17 patients suffering from iso-osmolar dehydration, where true data were obtained by balance studies. RESULTS: True and calculated data were compared with linear regression analysis. We obtained significant correlations both in computer-simulated and real patients (R(2) = 0.83, p < 0.005 and R(2) = 0.63, p < 0.05, respectively). CONCLUSION: This new math model and its related computational method are useful in the correct evaluation and treatment of iso-osmolar dehydration.

Gastric metastases. An endoscopic series of ten cases.

We report a series of ten cases of the clinical, endoscopic and pathological features of gastric metastases. Patients were six women and four men between 54 and 88 years old, with gastric metastases from breast carcinoma (4), lung carcinoma (4) and melanoma (2). Patients underwent an upper gastrointestinal endoscopy for epigastralgia (2), hematemesis (2), dysphagia (1) and anemia (5). On endoscopy, tumors appeared as nodules with a central ulceration (5), an ulceration (4) or simulating linitis plastica (1). Metastases were located in the cardia (2), fundus (5) and antrum (3). Primary tumors had been diagnosed between one day and 20 years before upper endoscopy. Eight patients had multivisceral metastases. The microscopic features of the gastric metastases resembled a primary gastric cancer in eight cases. Thanks to clinical data, the pathologist confirmed the diagnosis of gastric metastases on immunohistochemistry. Nine patients died in the eight-month follow-up period. Gastric metastases are rare, occur at a late stage of the neoplastic disease, and have a poor prognosis. Diagnosis of gastric metastases is difficult because they simulate primary gastric cancer on endoscopy and on microscopic examination. A correct diagnosis is based on good communication between gastroenterologists and pathologists.

[Embolization of recurrent bleeding jejunal varices]. / Embolisation de varices jéjunales hémorragiques récidivantes.

We report a case of recurrent digestive haemorrhage due to bleeding ectopic jejunal varices complicating portal hypertension in a 51-year-old cirrhotic patient, treated 1 year ago by transjugular intrahepatic porto-systemic shunt (TIPS) for the same problem. Successful embolisation with coils, of ectopic varices, was performed using original transjugular and trans-TIPS route, without complication, and no recurrence during a follow-up of 24 months.

Individuation of different metabolic phenotypes in normal glucose tolerance test.

Based on the hypothesis that a more efficient glucose utilization lowers the risk of progression to type 2 diabetes, we tested the capability of oral glucose tolerance test (OGTT) to identify subjects at risk included inside normal glucose tolerance (NGT). We measured fasting and 2-h plasma glucose (FPG and 2hPG) and insulin values (FPI and 2hPI) in 623 normal OGTTs. Insulin sensitivity and secretion were computed with HOMA2 method and Stumvoll's formula. Secretion was expressed as HOMA2%beta, first (1stPH) and second-phase (2ndPH) insulin release. The percentage increment of 2hPG with respect to FPG (PG%) was used to subdivide patients into PG% tertiles, considered as the primary grouping variable. Covariance analysis (ANCOVA) for multiple comparisons was performed considering the above measurements as dependent variables, sex, age, body mass index (BMI) and waist circumference as covariates. In subjects with PG% < or =0, we documented significant increments of insulin sensitivity and significant decrements of resistance and secretion compared to subjects with PG% >0. ANCOVA disclosed that insulin sensitivity fell, while 1stPH secretion rose significantly from the lower to the higher tertile of PG%. OGTT may be useful to establish NGT as well as a more subtle metabolic phenotype. The closer 2hPG is to FPG, the higher insulin sensitivity and the lower insulin secretion are. The stimulus to maintain NGT elicits more insulin secretion, predisposing to worsening glucose tolerance when a faltering insulin secretion ensues. These subjects could benefit from prospective prevention treatment and studies.

Quantitative assessment of the abnormalities of hyperosmolar coma when glucose excess is larger than Na deficit.

Computing Na and water deficits of hyperosmolar coma (HC) is important in correcting the derangement, to avoid unwanted iatrogenic electrolyte derangements and brain oedema. This paper derives and applies formulas valid when GA (glucose accumulation) >2.DeltaNa (sodium loss), with or without DeltaV (water depletion). We built a model system and wrote the equations describing the relationships between volume and concentration of solutes within the body water compartments. HC was simulated on computer experiments by adding GA in different amounts combined with a large variety of DeltaNa and DeltaV. The ensuing concentrations in Na (PNaNone. (1)) and glucose (PG (1)) were used to identify the condition GA >2 . DeltaNa, DeltaV=0 or not equal 0, and then, with original formulas, to back calculate GA, DeltaNa and DeltaV. These same calculations were applied to 31 patients with HC. The procedure to recognize the conditions under investigation unerringly discarded all simulations except those characterized by GA >2 . DeltaNa, with or without DeltaV. When DeltaV=0, the computations yielded values identical to the true ones for GA and DeltaNa (R (2)=1.00, p<0.0001). When DeltaV was present, the correlation coefficients between calculated and true values were 0.92 (p<0.001) for GA, 0.73 (p<0.001) for DeltaNa, 0.74 (p<0.001) for DeltaV in computer experiments, while they were R (2)>0.47<0.95 (p<0.001) in patient studies. The accuracy in computing solute and water changes demonstrates the validity of our model system of HC, and of the calculation formulas, which can be used to quantitatively evaluate the deficits in Na and volume, as well as the addition of glucose, improving the effectiveness of treatment.