Sequential maturation of stimulus-specific adaptation in the mouse lemniscal auditory system.

Stimulus-specific adaptation (SSA), the reduction of neural activity to a common stimulus that does not generalize to other, rare stimuli, is an essential property of our brain. Although well characterized in adults, it is still unknown how it develops during adolescence and what neuronal circuits are involved. Using in vivo electrophysiology and optogenetics in the lemniscal pathway of the mouse auditory system, we observed SSA to be stable from postnatal day 20 (P20) in the inferior colliculus, to develop until P30 in the auditory thalamus and even later in the primary auditory cortex (A1). We found this maturation process to be experience-dependent in A1 but not in thalamus and to be related to alterations in deep but not input layers of A1. We also identified corticothalamic projections to be implicated in thalamic SSA development. Together, our results reveal different circuits underlying the sequential SSA maturation and provide a unique perspective to understand predictive coding and surprise across sensory systems.

Under-Recognized Pathogens in Peritoneal Dialysis Associated-Peritonitis: The Importance of Early Detection.

Peritoneal dialysis-associated-peritonitis remains a major concern, increasing patient morbidity and mortality. Empirical antibiotics should be quickly started to allow a rapid resolution of symptoms and preservation of the peritoneal membrane. We report a case of peritoneal dialysis-associated-peritonitis due to Prevotella salivae and Corynebacterium jeikeium, in a 51-year-old male. Suspected peritonitis led to an immediate prescription of vancomycin and ceftazidime, with no clinical improvement. Prevotella is difficult to identify in culture since it's a gram-negative anaerobic bacterium, so metronidazole administration was delayed over days. New diagnostic techniques have been explored for the early diagnosis of peritonitis, including polymerase chain reaction (PCR) for bacterial DNA fragments. A multiplex PCR panel that includes Prevotella, already available for other applications, could be an advantage in cases like this.

SIRT2 Deficiency Exacerbates Hepatic Steatosis via a Putative Role of the ER Stress Pathway.

Nonalcoholic fatty liver disease (NAFLD), a condition strongly associated with obesity and insulin resistance, is characterized by hepatic lipid accumulation and activation of the endoplasmic reticulum (ER) stress response. The sirtuin 2 (SIRT2) protein deacetylase is emerging as a new player in metabolic homeostasis, but its role in the development of hepatic steatosis and its link with ER stress activation remains unknown. SIRT2-knockout (SIRT2-KO) and wild-type mice were fed either a control or a high-fat diet (HFD) for 4 weeks. Genetic manipulation of SIRT2 levels was performed in human hepatic cells. Although apparently normal under a control diet, SIRT2-KO mice showed accelerated body weight gain and adiposity on a HFD, accompanied by severe insulin resistance. Importantly, SIRT2-KO mice exhibited worsened hepatic steatosis independently from diet, consistent with upregulated gene expression of lipogenic enzymes and increased expression of ER stress markers. Exposure of hepatic cells to palmitate induced lipid accumulation, increased ER stress, and decreased SIRT2 expression. Moreover, SIRT2-silenced cells showed enhanced lipid accumulation and ER stress activation under basal conditions, whereas SIRT2 overexpression abrogated palmitate-induced lipid deposition and ER stress activation. Our findings reveal a role for SIRT2 in the regulation of hepatic lipid homeostasis, potentially through the ER stress response, suggesting that SIRT2 activation might constitute a therapeutic strategy against obesity and its metabolic complications.

The Law of Minimum Vertical Dimension: Evidence for Improvement of Dental Occlusion.

The law of minimum vertical dimension (MVD) states that "when the mandible moves to reach the maximum intercuspal position, this always involves bringing the mandible and maxilla as close together as possible." Therefore, after the first occlusal contact is made, the MIP will be reached through reduction of the vertical dimension. Our objective of this study, through an integrative review of the literature review, was to determine whether ignoring this law is a factor that contributes to malocclusion, temporomandibular joint dysfunction, and recurrences of functional orthodontic and orthopedic treatments.We conducted a search of the literature in five of the main electronic scientific databases. The following medical subject heading terms were used in our search: centric relation, dental occlusion, malocclusion, vertical dimension, and mastication. We cross-referenced the descriptors in the following four groups: centric relation and maximum intercuspation; occlusal plane and malocclusion; neuro-occlusal rehabilitation; and vertical dimension and unilateral chewing. From this, we selected 277 potentially eligible articles. Out of these, 209 were excluded in accordance with the exclusion criteria already described. Thus, 65 studies were included in the qualitative synthesis.The articles were also classified according to their impact factor and degree of recommendation, in conformity with the table of the Oxford Centre for Evidence-Based Medicine. The scientific interest in the scope of the articles was also assessed by using three charts developed according to year and country of publication and the percentage of publication. Unilateral chewing creates a vicious cycle of damage that leads to an ever-increasing masticatory deficiency. Most of the articles chosen for this review confirmed that noncompliance with law of MVD was a predisposing factor in cases of relapse, in functional orthodontic and orthopedic treatments, as well as a causal factor in malocclusion and in functional and morphological TMJ dysfunctions.

Frequency of Four-dimensional Oral Health Problems across Dental Fields - a Comparative Survey of Slovenian and International Dentists.

OBJECTIVES: To compare the frequency of patients' oral health problems and prevention needs among Slovenian and international dentists with the aim to validate the four oral health-related quality of life (OHRQoL) dimensions across six clinical dental fields in all World Health Organization (WHO) regions. METHODS: An anonymous electronic survey in the English language was designed using Qualtrics software. A probability sampling for Slovenia and a convenience sampling strategy for dentist recruitment was applied for 31 countries. Dentists engaged in six dental fields were asked to categorize their patients' oral health problems and prevention needs into the four OHRQoL dimensions (Oral Function, Orofacial Pain, Orofacial Appearance, and Psychosocial Impact). Proportions of patients' problems and prevention needs were calculated together with the significance of Slovenian and international dentists' differences based on dental fields and WHO regions. RESULTS: Dentists (n=1,580) from 32 countries completed the survey. There were 223 Slovenian dentists (females: 68%) with a mean age (SD) of 41 (10.6) years and 1,358 international dentists (females: 51%) with a mean age (SD) of 38 (10.4). Pain-related problems and prevention needs were the most prevalent among all six dental fields reported by dentists; Slovenian (37%) and 31 countries (45%). According to Cohen, differences between Slovenia, the broader European Region, and 31 countries were considered non-significant (<0.1). CONCLUSION: According to the dentists' responses, the frequency of patients' oral health problems and prevention needs are proportionate between Slovenia and 31 countries, regionally and globally. The four OHRQoL dimensions can be considered universal across all dental fields.

Pediatric patients' reasons for visiting dentists in all WHO regions.

BACKGROUND: Oral Function, Orofacial Pain, Orofacial Appearance, and Psychosocial Impact are the four oral health-related quality of life (OHRQoL) dimensions (4D) or areas in which oral disorders impact pediatric patients. Using their dentists' assessment, the study aimed to evaluate whether pediatric dental patients' oral health concerns fit into the 4D of the Oral Health-Related Quality of Life (OHRQoL) construct. METHODS: Dentists who treat children from 32 countries and all WHO regions were selected from a web-based survey of 1580 international dentists. Dentists were asked if their pediatric patients with current or future oral health concerns fit into the 4D of the Oral Health-Related Quality of Life (OHRQoL) construct. Proportions of all pediatric patients' oral health problems and prevention needs were computed. FINDINGS: Data from 101 dentists treating children only and 523 dentists treating children and adults were included. For 90% of pediatric patients, their current oral health problems fit well in the four OHRQoL dimensions. For 91% of oral health problems they intended to prevent in the future were related to these dimensions as well. Both numbers increased to at least 96% when experts analyzed dentists´ explanations of why some oral health problems would not fit these four categories. CONCLUSIONS: The study revealed the four fundamental components of dental patients, i.e., the four OHRQoL dimensions (Oral Function, Orofacial Pain, Orofacial Appearance, and Psychosocial Impact) are also applicable for pediatric patients, regardless of whether they have current or future oral health concerns, and should be considered when measuring OHRQoL in the pediatric dental patient population.

Thrombotic microangiopathy in oncology - a review.

Thrombotic microangiopathy is a syndrome triggered by a wide spectrum of situations, some of which are specific to the Oncology setting. It is characterized by a Coombs-negative microangiopathic haemolytic anemia, thrombocytopenia and organ injury, with characteristic pathological features, resulting from platelet microvascular occlusion. TMA is rare and its cancer-related subset even more so. TMA triggered by drugs is the most common within this group, including classic chemotherapy and the latest targeted therapies. The neoplastic disease itself and hematopoietic stem-cell transplantation could also be potential triggers. Evidence-based medical guidance in the management of cancer-related TMA is scarce and the previous knowledge about primary TMA is valuable to understand the disease mechanisms and the potential treatments. Given the wide spectrum of potential causes for TMA in cancer patients, the aim of this review is to gather the vast information available. For each entity, pathophysiology, clinical features, therapeutic approaches and prognosis will be covered.

Use of Peritoneal Catheters for Patients Receiving Palliative Care.

Background: Recurrent ascites is a late manifestation of several diseases, including cancer, cirrhosis, and heart failure, invariably associated with very poor prognosis. Hence, every effort must be aimed at reducing discomfort and side effects of its management. Objective: To evaluate if peritoneal catheters (PCs) are a viable alternative treatment approach in palliative patients who fail medical management of ascites. Design: Case study. Results: We report the case of a terminal patient with cirrhosis and hepatocellular carcinoma who presented refractory ascites despite serial large-volume paracentesis. A Tenckhoff percutaneous catheter was inserted, allowing for ascites' control and with no complications noted. Conclusions: PC placement was successful in controlling the patient's symptoms and ultimately improved comfort and well-being during the final stage of his life. This option should be assessed in selected patients to elevate palliative standards of care.

Why Patients Visit Dentists - A Study in all World Health Organization Regions.

OBJECTIVE: The dimensions of oral health-related quality of life (OHRQoL) Oral Function, Orofacial Pain, Orofacial Appearance, and Psychosocial Impact are the major areas where patients are impacted by oral diseases and dental interventions. The aim of this study was to evaluate whether dental patients' reasons to visit the dentist fit the 4 OHRQoL dimensions. METHODS: Dentists (N = 1580) from 32 countries participated in a web-based survey. For their patients with current oral health problems, dentists were asked whether these problems were related to teeth, mouth, and jaws' function, pain, appearance, or psychosocial impact or whether they do not fit the aforementioned 4 categories. Dentists were also asked about their patients who intended to prevent future oral health problems. For both patient groups, the proportions of oral health problems falling into the 4 OHRQoL dimensions were calculated. RESULTS: For every 100 dental patients with current oral health problems, 96 had problems related to teeth, mouth, and jaws' function, pain, appearance, or psychosocial impact. For every 100 dental patients who wanted to prevent future oral health problems, 92 wanted to prevent problems related to these 4 OHRQoL dimensions. Both numbers increased to at least 98 of 100 patients when experts analyzed dentists' explanations of why some oral health problems would not fit the four dimension. For the remaining 2 of 100 patients, none of the dentist-provided explanations suggested evidence against the OHRQoL dimensions as the concepts that capture dental patients' suffering. CONCLUSION: Oral Function, Orofacial Pain, Orofacial Appearance, and Psychosocial Impact capture dental patients' oral health problems worldwide. These 4 OHRQoL dimensions offer a psychometrically sound and practical framework for patient care and research, identifying what is important to dental patients.

Sequential Organization of Critical Periods in the Mouse Auditory System.

Critical periods-time windows of heightened plasticity in postnatal development-are specific to sensory features and are asynchronous. Whether they are timed by a temporally precise developmental program or are sequentially organized is not known. We use electrophysiology and molecular or sensory manipulations to elucidate the biological constraints on critical period timing. Passive sound exposure shows that the cortical representations of two sound features, pure tone and frequency-modulated sweep (FMS), are not influencing each other. Enhancing inhibition before the critical period for pure tone accelerates it without changing the critical period for FMS. Similarly, delaying the critical period for pure tone with white noise exposure has no effect on the critical period for FMS. However, the critical period for FMS starts only if the one for pure tone has occurred. Together, these results indicate that distinct critical periods, although sequentially organized, can be temporally shifted independently of each other.

Hemodialysis Catheter-Related Thrombi: A Challenging Patient.

Patients requiring renal replacement therapy remain a significant burden on the healthcare system. A substantial amount of hospitalization costs for these patients are related to vascular complications, especially catheter-related thrombosis, which is associated with a significant increase in morbidity and mortality. We report the case of a male patient with multiple myeloma (MM) and dialysis-dependent renal failure due to light-chain cast nephropathy, who presented recurrent early catheter dysfunction. A large thrombus was detected, extending from the superior vena cava (SVC) to the right atrium (RA) and later at the inferior vena cava (IVC), ultimately leading to exhaustion of vascular capital. To this date, there is limited evidence regarding the best approach to catheter-related thrombosis, which frequently leads to treatment dilemmas in clinical practice and demands careful evaluation and individualized decisions. In patients with a highly thrombotic profile, peritoneal dialysis may be considered earlier to prevent further vascular capital damage.

An unexpected cause of residual renal function loss.

The residual renal function (RRF) in a peritoneal dialysis (PD) patient is clinically important because it contributes to dialytic adequacy, quality of life and mortality. We present the case of a patient in PD with a marked decrease in RRF. Even after the increase of dialysis, the patient maintained asthenia and anorexia, was prostrate and showed no improvement analytically. The study revealed hypothyroidism, iatrogenic due to the use of amiodarone. After suspension of the drug and replacement with levothyroxine, there was a normalization of thyroid function and recovery of RRF to baseline values. A thyroid dysfunction is associated with several changes in renal function, in most cases reversible after obtaining euthyroid state. The association between thyroid dysfunction and loss of RRF continues to be under-recognized. We should consider monitoring thyroid function annually as routine in this group of patients.

A Late Critical Period for Frequency Modulated Sweeps in the Mouse Auditory System.

Neuronal circuits are shaped by experience during time windows of increased plasticity in postnatal development. In the auditory system, the critical period for the simplest sounds-pure frequency tones-is well defined. Critical periods for more complex sounds remain to be elucidated. We used in vivo electrophysiological recordings in the mouse auditory cortex to demonstrate that passive exposure to frequency modulated sweeps (FMS) from postnatal day 31 to 38 leads to long-term changes in the temporal representation of sweep directions. Immunohistochemical analysis revealed a decreased percentage of layer 4 parvalbumin-positive (PV+) cells during this critical period, paralleled with a transient increase in responses to FMS, but not to pure tones. Preventing the PV+ cell decrease with continuous white noise exposure delayed the critical period onset, suggesting a reduction in inhibition as a mechanism for this plasticity. Our findings shed new light on the dependence of plastic windows on stimulus complexity that persistently sculpt the functional organization of the auditory cortex.

p53 in AgRP neurons is required for protection against diet-induced obesity via JNK1.

p53 is a well-known tumor suppressor that has emerged as an important player in energy balance. However, its metabolic role in the hypothalamus remains unknown. Herein, we show that mice lacking p53 in agouti-related peptide (AgRP), but not proopiomelanocortin (POMC) or steroidogenic factor-1 (SF1) neurons, are more prone to develop diet-induced obesity and show reduced brown adipose tissue (BAT) thermogenic activity. AgRP-specific ablation of p53 resulted in increased hypothalamic c-Jun N-terminal kinase (JNK) activity before the mice developed obesity, and central inhibition of JNK reversed the obese phenotype of these mice. The overexpression of p53 in the ARC or specifically in AgRP neurons of obese mice decreased body weight and stimulated BAT thermogenesis, resulting in body weight loss. Finally, p53 in AgRP neurons regulates the ghrelin-induced food intake and body weight. Overall, our findings provide evidence that p53 in AgRP neurons is required for normal adaptations against diet-induced obesity.

Outcomes of acute kidney injury in a nephrology ward.

Acute kidney injury (AKI) is a global problem which predicts immediate and long-term adverse outcomes. We evaluated the AKI progression to end-stage renal disease, as well as the mortality associated with AKI and the in-hospital readmission rate because of a cardiovascular event in AKI patients admitted in a nephrology ward. A 5-year retrospective study was set in a nephrology department, with a follow-up period of up to 8 years. In a total of 191 patients, mean age was 73.83 ± 12.49 years, and 137 (71.7%) patients had history of chronic kidney disease. One hundred and twenty-four (65%) patients needed RRT and two (1%) needed surgery. Upon discharge, 107 (56%) patients had recovered the renal function, 41 (21.6%) patients had partial recovery, 25 (13%) patients were RRT dependent, 16 (8.4%) died, and two (1%) patients had outcomes unknown to us, because they were transferred to other hospitals. The median survival time free of RRT was 74 months. The median survival time of the followed patients was 34 months (95% CI 23.3-44.7). The mortality rate in the follow-up period in this sample was 18 deaths/100 patients-years, and the incidence of a composite cardiovascular endpoint of heart failure, acute coronary syndrome, and stroke was 6 events/100 patients-years. The mortality rate in the follow-up period was higher than usually described for patients outside intensive care unit, probably because our patients were old and had many comorbidities.