Acute Hypophagia and Changes in c-Fos Immunoreactivity in Adolescent Rats Treated with Low Doses of Oxytocin and Naltrexone

A recent case report has shown that an adjunctive oxytocin + naltrexone (OT + NTX) treatment promoted more robust hypophagia and body weight reduction than OT alone in an adolescent male with hypothalamic obesity after craniopharyngioma resection. Thus far, there has been no basic research in adolescent laboratory animals that would examine whether the benefit of OT + NTX on appetite extends onto adolescent individuals without surgically induced overeating. Thus, here we examined whether low doses of combined OT + NTX acutely affect post-deprivation intake of energy-dense, standard chow; intake of energy-dense and palatable high-fat high-sugar (HFHS) diet; or calorie-dilute, palaTable 10% sucrose solution without deprivation in adolescent male rats. We assessed whether OT + NTX decreases water intake after water deprivation or produces a conditioned taste aversion (CTA). Finally, by using c-Fos immunoreactivity, we determined changes in activity of feeding-related brain areas after OT + NTX. We found that individual subthreshold doses of OT and NTX decreased feeding induced by energy and by palatability. Significant c-Fos changes were noted in the arcuate and dorsomedial hypothalamic nuclei. The hypophagic doses of OT + NTX did not suppress water intake in thirsty rats and did not cause a CTA, which suggests that feeding reduction is not a secondary effect of gastrointestinal discomfort or changes in thirst processing. We conclude that OT + NTX is an effective drug combination to reduce appetite in adolescent male rats.

NEUROD1 Mutation in an Italian Patient With Maturity Onset Diabetes of the Young 6: a Case Report

Background and Aims: maturity onset diabetes of the young (MODY) is a monogenic, autosomal, dominant disease characterized by a single genetic mutation that results in beta-cells disfunction with consequent hyperglycemia. It represents a rare form of diabetes (1-2% of all the cases). Sulphonylureas (SU) represent the first line treatment for this form of diabetic disease. NEUROD1 is a transcription factor expressed by pancreatic and nervous tissues that is necessary for a proper development of beta cells. A mutation of NEUROD1 gene has been found to cause beta-cells dysfunction, inadequate insulin secretion, and hyperglycemia (MODY 6). A recent case report has documented for the first time a new missense mutation (p.Met114Leu c.340A> C), of the NEUROD1 gene pathogenetic for diabetes mellitus.Methods and Results: We report the case of a 50 years-old man who presented the same mutation, and who was able to suspend rapid insulin after the diagnosis and treatment with SU. Interestingly, our patient had an early onset dilated cardiomyopathy but no other data about cardiac diseases in patients with MODY 6 are available.Conclusions: Diagnostic criteria for MODY can overlap with other kinds of diabetes and most cases are still misdiagnosed as diabetes type 1 or 2. The disease should be suspected in patients with a strong family history of diabetes, normal BMI, early onset and no autoimmunity.

Bi-allelic TTC5 variants cause delayed developmental milestones and intellectual disability

BackgroundIntellectual disability syndromes (IDSs) with or without developmental delays affect up to 3% of the world population. We sought to clinically and genetically characterise a novel IDS segregating in five unrelated consanguineous families.MethodsClinical analyses were performed for eight patients with intellectual disability (ID). Whole-exome sequencing for selected participants followed by Sanger sequencing for all available family members was completed. Identity-by-descent (IBD) mapping was carried out for patients in two Egyptian families harbouring an identical variant. RNA was extracted from blood cells of Turkish participants, followed by cDNA synthesis and real-time PCR for TTC5.ResultsPhenotype comparisons of patients revealed shared clinical features of moderate-to-severe ID, corpus callosum agenesis, mild ventriculomegaly, simplified gyral pattern, cerebral atrophy, delayed motor and verbal milestones and hypotonia, presenting with an IDS. Four novel homozygous variants in TTC5: c.629A>G;p.(Tyr210Cys), c.692C>T;p.(Ala231Val), c.787C>T;p.(Arg263Ter) and c.1883C>T;p.(Arg395Ter) were identified in the eight patients from participating families. IBD mapping revealed that c.787C>T;p.(Arg263Ter) is a founder variant in Egypt. Missense variants c.629A>G;p.(Tyr210Cys) and c.692C>T;p.(Ala231Val) disrupt highly conserved residues of TTC5 within the fifth and sixth tetratricopeptide repeat motifs which are required for p300 interaction, while the nonsense variants are predicted to decrease TTC5 expression. Functional analysis of variant c.1883C>T;p.(Arg395Ter) showed reduced TTC5 transcript levels in accordance with nonsense-mediated decay.ConclusionCombining our clinical and molecular data with a recent case report, we identify the core and variable clinical features associated with TTC5 loss-of-function variants and reveal the requirement for TTC5 in human brain development and health.

Emerging Coronavirus Disease (COVID-19), a Pandemic Public Health Emergency with Animal Linkages: Current Status Update

After the appearance of first cases of ‘pneumonia of unknown origin’ in the Wuhan city, China, during late 2019, the disease progressed fast. Its cause was identified as a novel coronavirus, named provisionally 2019-nCoV. Subsequently, an official name was given as SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) by the International Committee on Taxonomy of Viruses (ICTV) study group. The World Health Organization (WHO) named the Coronavirus disease-2019 as COVID-19. The epidemics of COVID-2019 have been recorded over 113 countries/territories/areas apart from China and filched more than 4292 humans, affecting severely around 1,18,326 cases in a short span. The status of COVID-2019 emergency revised by the WHO within 42 days from Public Health International Emergency (January 30, 2020) to a pandemic (March 11, 2020). Nonetheless, the case fatality rate (CFR) of the current epidemic is on the rise (between 2-4%), relatively is lower than the previous SARS-CoV (2002/2003) and MERS-CoV (2012) outbreaks. Even though investigations are on its way, the researchers across the globe have assumptions of animal-origin of current SARS-CoV-2. A recent case report provides evidence of mild COVID-2019 infection in a pet dog that acquired COVID-2019 infection from his owner in Hong Kong. The news on travellers associated spread across the globe have also put many countries on alert with the cancellation of tourist visa to all affected countries and postponement of events where international visits were required. A few diagnostic approaches, including quantitative and differential real-time polymerase chain reaction assays, have been recommended for the screening of the individuals at risk. In the absence of any selective vaccine against SARS-CoV-2, re-purposed drugs are advocated in many studies. This article discourse the current worldwide situation of COVID-2019 with information on virus, epidemiology, host, the role of animals, effective diagnosis, therapeutics, preventive and control approaches making people aware on the disease outcomes.

Aggressive Surgical Management of Spontaneous Intramuscular Haematomas in Patients with Cirrhosis is an Important Therapeutic Option

One known medical complication in patients with cirrhosis of the liver is sudden onset gastrointestinal haemorrhage which is usually variceal in nature and can be life threatening [1]. On occasion spontaneous haemorrhage from varices in other locations may also occur [2]. In addition, episodes of either intraabdominal or intrapulmonary haemorrhage are also associated with poor clinical outcomes in cirrhotic patients [3,4]. In comparison relatively, few cases of spontaneous intramuscular haemorrhage in patients with cirrhosis have been reported up to now. This particular clinical entity has been predominantly the subject of sporadic case reports or case series. Apart from one small case series [5], the majority of the cases were summarised in a published review in 2015 [6]. Hence the most recent case report from Mongelli et al published recently in this journal [7], now becomes the 25th case. Keywords: Cirrhosis; Spontaneous; Haemorrhage; Intramuscular; Management; Surgery

Pulseless electrical activity: a misdiagnosed entity during asphyxia in newborn infants?

BackgroundThe 2015 neonatal resuscitation guidelines added ECG as a recommended method of assessment of an infant’s heart rate (HR) when determining the need for resuscitation at birth. However, a recent case report raised concerns about this technique in the delivery room.ObjectivesTo compare accuracy of ECG with auscultation to assess asystole in asphyxiated piglets.MethodsNeonatal piglets had the right common carotid artery exposed and enclosed with a real-time ultrasonic flow probe and HR was continuously measured and recorded using ECG. This set-up allowed simultaneous monitoring of HR via ECG and carotid blood flow (CBF). The piglets were exposed to 30 min normocapnic alveolar hypoxia followed by asphyxia until asystole, achieved by disconnecting the ventilator and clamping the endotracheal tube. Asystole was defined as zero carotid blood flow and was compared with ECG traces and auscultation for heart sounds using a neonatal/infant stethoscope.ResultsOverall, 54 piglets were studied with a median (IQR) duration of asphyxia of 325 (200-491) s. In 14 (26%) piglets, CBF, ECG and auscultation identified asystole. In 23 (43%) piglets, we observed no CBF and no audible heart sounds, while ECG displayed an HR ranging from 15 to 80/min. Sixteen (30%) piglets remained bradycardic (defined as HR of <100/min) after 10 min of asphyxia, identified by CBF, ECG and auscultation.ConclusionClinicians should be aware of the potential inaccuracy of ECG assessment during asphyxia in newborn infants and should rather rely on assessment using a combination of auscultation, palpation, pulse oximetry and ECG.

Short but Continuous Natural Pain for Depression Treatment and Beyond

The correlation and comorbidity between depression and chronic pain have been observed for a long time. Generally, it is considered that the two conditions reinforce each other, whereas the causal relationship between them is not clear. However, some evidence suggested that chronic pain may reverse the progression of depression in some cases. This article presents a selective review of clinical and pharmacological relationship between depression and pain, and their interactions at neurochemical and neurobiological levels. In addition, we open a discussion on a recent case report of repeated success of using short but continuous pain (SCP) during meditation as the only treatment for depression, compared to initial success but no remission with other conventional antidepressants on the same patient. Together this review proposes an updated model for depression and its various treatments that is based on synaptic and system homeostasis. More importantly, it suggests that SCP may benefit depression recovery through its properties that are different from either acute or chronic pain and represents a novel research area that has been largely neglected to date.

Short but Continuous Natural Pain for Depression Treatment and Beyond

The correlation and comorbidity between depression and chronic pain have been observed for a long time. Generally, it is considered that the two conditions reinforce each other, whereas the causal relationship between them is not clear. However, some evidence suggested that chronic pain may reverse the progression of depression in some cases. This article presents a selective review of clinical and pharmacological observations between depression and pain, and their interactions at neurochemical and neurobiological levels. In addition, we open a discussion on a recent case report of repeated success of using short but continuous pain during meditation as the only treatment of depression, compared to initial success but no remission with other conventional antidepressants on the same patient. Together this review proposes an updated model for depression and its various treatments that is based on synaptic and system homeostasis. More importantly, it suggests that short but continuous pain may benefit depression recovery through its properties that are different from either acute or chronic pain and represents a novel research area that has been largely neglected to date.