The Role of Parvalbumin Interneurons in Neurotransmitter Balance and Neurological Disease

While great progress has been made in the understanding of neurological illnesses, the pathologies, and etiologies that give rise to these diseases still remain an enigma, thus, also making treatments for them more challenging. For effective and individualized treatment, it is beneficial to identify the underlying mechanisms that govern the associated cognitive and behavioral processes that go awry in neurological disorders. Parvalbumin fast-spiking interneurons (Pv-FSI) are GABAergic cells that are only a small fraction of the brain's neuronal network, but manifest unique cellular and molecular properties that drastically influence the downstream effects on signaling and ultimately change cognitive behaviors. Proper brain functioning relies heavily on neuronal communication which Pv-FSI regulates, excitatory-inhibitory balances and GABAergic disinhibition between circuitries. This review highlights the depth of Pv-FSI involvement in the cortex, hippocampus, and striatum, as it pertains to expression, neurotransmission, role in neurological disorders, and dysfunction, as well as cognitive behavior and reward-seeking. Recent research has indicated that Pv-FSI play pivotal roles in the molecular pathophysiology and cognitive-behavioral deficits that are core features of many psychiatric disorders, such as schizophrenia, autism spectrum disorders, Alzheimer's disease, and drug addiction. This suggests that Pv-FSI could be viable targets for treatment of these disorders and thus calls for further examination of the undeniable impact Pv-FSI have on the brain and cognitive behavior

Benzodiazepines: Uses, dangers, and clinical considerations

Benzodiazepines (BZDs) are among one of the most widely prescribed drug classes in the United States. BZDs are a class of psychoactive drugs known for their depressant effect on the central nervous system (CNS). They quickly diffuse through the blood–brain barrier to affect the inhibitory neurotransmitter GABA and exert sedative effects. Related to their rapid onset and immediate symptom relief, BZDs are used for those struggling with sleep, anxiety, spasticity due to CNS pathology, muscle relaxation, and epilepsy. One of the debilitating side effects of BZDs is their addictive potential. The dependence on BZDs generally leads to withdrawal symptoms, requiring careful tapering of the medication when prescribed. Regular use of BZDs has been shown to cause severe, harmful psychological and physical dependence, leading to withdrawal symptoms similar to that of alcohol withdrawal. Some of these withdrawal symptoms can be life threatening. The current treatment for withdrawal is through tapering with clonazepam. Many drugs have been tested as a treatment for withdrawal, with few proving efficacious in randomized control trials. Future research is warranted for further exploration into alternative methods of treating BZD withdrawal. This call to action proves especially relevant, as those seeking treatment for BZD dependence and withdrawal are on the rise in the United States

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Benzodiazepines: uses, dangers, and clinical considerations.

Benzodiazepines (BZDs) are among one of the most widely prescribed drug classes in the United States. BZDs are a class of psychoactive drugs known for their depressant effect on the central nervous system (CNS). They quickly diffuse through the blood-brain barrier to affect the inhibitory neurotransmitter GABA and exert sedative effects. Related to their rapid onset and immediate symptom relief, BZDs are used for those struggling with sleep, anxiety, spasticity due to CNS pathology, muscle relaxation, and epilepsy. One of the debilitating side effects of BZDs is their addictive potential. The dependence on BZDs generally leads to withdrawal symptoms, requiring careful tapering of the medication when prescribed. Regular use of BZDs has been shown to cause severe, harmful psychological and physical dependence, leading to withdrawal symptoms similar to that of alcohol withdrawal. Some of these withdrawal symptoms can be life threatening. The current treatment for withdrawal is through tapering with clonazepam. Many drugs have been tested as a treatment for withdrawal, with few proving efficacious in randomized control trials. Future research is warranted for further exploration into alternative methods of treating BZD withdrawal. This call to action proves especially relevant, as those seeking treatment for BZD dependence and withdrawal are on the rise in the United States

Benzodiazepines: Uses, Dangers, and Clinical Considerations

Benzodiazepines (BZDs) are among one of the most widely prescribed drug classes in the United States. BZDs are a class of psychoactive drugs known for their depressant effect on the central nervous system (CNS). They quickly diffuse through the blood–brain barrier to affect the inhibitory neurotransmitter GABA and exert sedative effects. Related to their rapid onset and immediate symptom relief, BZDs are used for those struggling with sleep, anxiety, spasticity due to CNS pathology, muscle relaxation, and epilepsy. One of the debilitating side effects of BZDs is their addictive potential. The dependence on BZDs generally leads to withdrawal symptoms, requiring careful tapering of the medication when prescribed. Regular use of BZDs has been shown to cause severe, harmful psychological and physical dependence, leading to withdrawal symptoms similar to that of alcohol withdrawal. Some of these withdrawal symptoms can be life threatening. The current treatment for withdrawal is through tapering with clonazepam. Many drugs have been tested as a treatment for withdrawal, with few proving efficacious in randomized control trials. Future research is warranted for further exploration into alternative methods of treating BZD withdrawal. This call to action proves especially relevant, as those seeking treatment for BZD dependence and withdrawal are on the rise in the United States

Benzodiazepines: Uses, dangers, and clinical considerations

Benzodiazepines (BZDs) are among one of the most widely prescribed drug classes in the United States. BZDs are a class of psychoactive drugs known for their depressant effect on the central nervous system (CNS). They quickly diffuse through the blood–brain barrier to affect the inhibitory neurotransmitter GABA and exert sedative effects. Related to their rapid onset and immediate symptom relief, BZDs are used for those struggling with sleep, anxiety, spasticity due to CNS pathology, muscle relaxation, and epilepsy. One of the debilitating side effects of BZDs is their addictive potential. The dependence on BZDs generally leads to withdrawal symptoms, requiring careful tapering of the medication when prescribed. Regular use of BZDs has been shown to cause severe, harmful psychological and physical dependence, leading to withdrawal symptoms similar to that of alcohol withdrawal. Some of these withdrawal symptoms can be life threatening. The current treatment for withdrawal is through tapering with clonazepam. Many drugs have been tested as a treatment for withdrawal, with few proving efficacious in randomized control trials. Future research is warranted for further exploration into alternative methods of treating BZD withdrawal. This call to action proves especially relevant, as those seeking treatment for BZD dependence and withdrawal are on the rise in the United States

Respiratory support in patients with severe COVID-19 in the International Severe Acute Respiratory and Emerging Infection (ISARIC) COVID-19 study: a prospective, multinational, observational study

Background: Up to 30% of hospitalised patients with COVID-19 require advanced respiratory support, including high-flow nasal cannulas (HFNC), non-invasive mechanical ventilation (NIV), or invasive mechanical ventilation (IMV). We aimed to describe the clinical characteristics, outcomes and risk factors for failing non-invasive respiratory support in patients treated with severe COVID-19 during the first two years of the pandemic in high-income countries (HICs) and low middle-income countries (LMICs). Methods: This is a multinational, multicentre, prospective cohort study embedded in the ISARIC-WHO COVID-19 Clinical Characterisation Protocol. Patients with laboratory-confirmed SARS-CoV-2 infection who required hospital admission were recruited prospectively. Patients treated with HFNC, NIV, or IMV within the first 24 h of hospital admission were included in this study. Descriptive statistics, random forest, and logistic regression analyses were used to describe clinical characteristics and compare clinical outcomes among patients treated with the different types of advanced respiratory support. Results: A total of 66,565 patients were included in this study. Overall, 82.6% of patients were treated in HIC, and 40.6% were admitted to the hospital during the first pandemic wave. During the first 24 h after hospital admission, patients in HICs were more frequently treated with HFNC (48.0%), followed by NIV (38.6%) and IMV (13.4%). In contrast, patients admitted in lower- and middle-income countries (LMICs) were less frequently treated with HFNC (16.1%) and the majority received IMV (59.1%). The failure rate of non-invasive respiratory support (i.e. HFNC or NIV) was 15.5%, of which 71.2% were from HIC and 28.8% from LMIC. The variables most strongly associated with non-invasive ventilation failure, defined as progression to IMV, were high leukocyte counts at hospital admission (OR [95%CI]; 5.86 [4.83–7.10]), treatment in an LMIC (OR [95%CI]; 2.04 [1.97–2.11]), and tachypnoea at hospital admission (OR [95%CI]; 1.16 [1.14–1.18]). Patients who failed HFNC/NIV had a higher 28-day fatality ratio (OR [95%CI]; 1.27 [1.25–1.30]). Conclusions: In the present international cohort, the most frequently used advanced respiratory support was the HFNC. However, IMV was used more often in LMIC. Higher leucocyte count, tachypnoea, and treatment in LMIC were risk factors for HFNC/NIV failure. HFNC/NIV failure was related to worse clinical outcomes, such as 28-day mortality. Trial registration This is a prospective observational study; therefore, no health care interventions were applied to participants, and trial registration is not applicable

The value of open-source clinical science in pandemic response: lessons from ISARIC

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