Characteristics of Imperial College London's COVID-19 research outputs.

We identified 651 research outputs on the topic of COVID-19 in the form of preprint, report, journal article, dataset, and software/code published by Imperial College London authors between January to September 2020. We sought to understand the distribution of outputs over time by output type, peer review status, publisher, and open access status. Search of Scopus, the institutional repositories, Github, and other databases identified relevant research outputs, which were then combined with Unpaywall open access data and manually-verified associations between preprints and journal articles. Reports were the earliest output to emerge [median: 103 days, interquartile range (IQR): 57.5-129], but journal articles were the most commonly occurring output type over the entire period (60.8%, 396/651). Thirty preprints were identified as connected to a journal article within the set (15.8%, 30/189). A total of 52 publishers were identified, of which 4 publishers account for 59.6% of outputs (388/651). The majority of outputs were available open access through gold, hybrid, or green route (66.1%, 430/651). The presence of exclusively non-peer reviewed material from January to March suggests that demand could not be met by journals in this period, and the sector supported this with enhanced preprint services for authors. Connections between preprints and published articles suggests that some authors chose to use both dissemination methods and that, as some publishers also serve across both models, traditional distinctions of output types might be changing. The bronze open access cohort brings widespread 'free' access but does not ensure true open access.

CCDC141 Mutation Identified in Anosmic Hypogonadotropic Hypogonadism (Kallmann Syndrome) Alters GnRH Neuronal Migration.

The first mutation in a gene associated with a neuronal migration disorder was identified in patients with Kallmann Syndrome, characterized by hypogonadotropic hypogonadism and anosmia. This pathophysiological association results from a defect in the development of the GnRH and the olfactory system. A recent genetic screening of Kallmann Syndrome patients revealed a novel mutation in CCDC141. Little is known about CCDC141, which encodes a coiled-coil domain containing protein. Here, we show that Ccdc141 is expressed in GnRH neurons and olfactory fibers and that knockdown of Ccdc141 reduces GnRH neuronal migration. Our findings in human patients and mouse models predict that CCDC141 takes part in embryonic migration of GnRH neurons enabling them to form a hypothalamic neuronal network to initiate pulsatile GnRH secretion and reproductive function.

Studies on the reproductive effects of chronic treatment with agomelatine in the rat.

Agomelatine is an antidepressant with a novel mechanism of action. It is a melatonergic agonist for MT1 and MT2 receptors and a serotonin (5-HT2C) receptor antagonist. Agomelatine has been suggested not to have adverse effects on sexual functions. However, the effects of chronic agomelatine administration on reproductive functions have not been sufficiently studied in animal models. We mainly aimed to explore the effects of agomelatine on reproductive functions in the male and female rats. For the experimental studies, Sprague Dawley rats were used. The animals started to receive daily oral agomelatine (10mg/kg) on post-natal day 21. Agomelatine advanced vaginal opening in the female rats whereas it delayed puberty onset in the male rats. Agomelatine treatment significantly decreased intromission frequencies, which indicates a facilitator role of this antidepressant on male sexual behavior. In the forced swimming test (FST) used for assessing antidepressant efficacy, agomelatine induced a significant decrease in duration of immobility, and an increase in the swimming time, respectively, which confirms the antidepressant-like activity of agomelatine. The present findings suggest that agomelatine shows a strong antidepressant effect in the male rats without any adverse influences on sexual behavior, and its effects on pubertal maturation seem to show sex-dependent differences.

Serum apelin levels in patients with thyroid dysfunction.

Adipocytes are not only for energy storage, but are also functionally active cells, producing biologically active peptides called adipocytokines. Adipocytokines control nutrition, thermogenesis, immunity, thyroid and reproductive hormones, and neuroendocrine functions. One of the most important new members of this family is apelin. In patients with thyroid dysfunctions, there are usually changes in weight, thermogenesis and adipose tissue lipolysis. Here, we investigated the serum apelin levels in different thyroid hormone states. Our study group consisted of the following patients: 32 thyrotoxicosis, 32 subclinical hyperthyroidism, 31 hypothyroidism, 34 subclinical hypothyroidism and 31 healthy control cases. In addition to routine blood tests, serum free T3 (FT3), free T4 (FT4), TSH and apelin levels were measured, and the body mass index (BMI) was recorded. In terms of the demographic characteristics, age and BMI, there was no statistically significant difference between the groups (P>0.05). The mean serum apelin levels of the groups were as follows: thyrotoxicosis group, 4.6±1.9 ng/ml; subclinical hyperthyroidism group, 3.7±1.9 ng/ml; hypothyroid group, 4.8±2.5 ng/ml; subclinical hypothyroidism group, 4.3±2.2 ng/mL; and control group, 3.4±1.4 ng/ml, respectively. There was no statistically significant difference in terms of the mean apelin levels between the groups (P>0.05). The hypothyroid group had the highest and the control group had the lowest mean apelin levels. As a result, the apelin levels were higher in both the patients with hypothyroidism and hyperthyroidism, in comparison with the normal population, but without statistical significance.

Beneficial effects of training at the anaerobic threshold in addition to pharmacotherapy on weight loss, body composition, and exercise performance in women with obesity.

OBJECTIVE: The aim of this study was to determine and compare the effects of weight loss achieved through orlistat therapy alone or a combination of orlistat and an aerobic exercise training program on aerobic fitness and body composition in obese females. METHODS: Twenty-eight obese patients were randomly assigned to receive 12-week treatment with hypocaloric diet-orlistat or diet-orlistat-exercise. Each participant performed an incremental ramp exercise test every 4 weeks to measure aerobic fitness. Fourteen participants performed continuous exercise (approximately 45 minutes per session) at a work rate corresponding to the anaerobic threshold three times per week. RESULTS: A decrease in the fat mass to body weight ratio of 3.8% (P=0.006) was observed at the end of the 12 weeks in the orlistat group, while a decrease of 9.5% (P=0.001) was seen in the orlistat-exercise group. Maximal exercise capacity increased by 46.5% in the orlistat-exercise group and by 19.5% in the orlistat group. CONCLUSION: While orlistat therapy resulted in an improvement in body composition and aerobic fitness at the end of the 12-week period, its combination with exercise training provided improvements in the same parameters within the first 4 weeks of the study. These additional beneficial effects of combining aerobic exercise with orlistat therapy are important with regards to obesity-associated risk factors.

Increased serum prolactin in borderline personality disorder.

Although there is an important interaction between serotonergic system, prolactin and suicidal behavior, and impulsivity, no investigation examined the prolactin values in borderline personality disorder in which suicidal behavior and impulsivity are core symptom dimensions. In this context, in the present investigation, we planned to measure serum prolactin levels in the patients with borderline personality disorder. The study comprised 15 patients with borderline personality disorder and 15 healthy controls. Prolactin values were measured in both patients and control subjects. The patients had abnormally higher mean value of prolactin compared to those of healthy controls (48.66 ± 36.48 mg/dl for patients vs. 15.20 ± 7.81 mg/dl for healthy controls). There was no correlation between prolactin values and any demographic variables for both the patients and control subjects. In conclusion, our present results suggest that prolactin values increased in the patients with borderline personality disorder and are required to be replicated by more comprehensive and detailed further studies to decipher the exact roles of prolactin increase.

A Pregnant Woman Who Underwent Laparoscopic Adrenalectomy due to Cushing's Syndrome.

Cushing's syndrome (CS) may lead to severe maternal and fetal morbidities and even mortalities in pregnancy. However, pregnancy complicates the diagnosis and treatment of CS. This study describes a 26-year-old pregnant woman admitted with hypertension-induced headache. Hormonal analyses performed due to her cushingoid phenotype revealed a diagnosis of adrenocorticotropic hormone- (ACTH-) independent CS. MRI showed a 3.5 cm adenoma in her right adrenal gland. After preoperative metyrapone therapy, she underwent a successful unilateral laparoscopic adrenalectomy at 14-week gestation. Although she had a temporary postoperative adrenal insufficiency, hormonal analyses showed that she has been in remission since delivery. Findings in this patient, as well as those in previous patients, indicate that pregnancy is not an absolute contraindication for laparoscopic adrenalectomy. Rather, such surgery should be considered a safe and efficient treatment method for pregnant women with cortisol-secreting adrenal adenomas.

Mutations in FEZF1 cause Kallmann syndrome.

Gonadotropin-releasing hormone (GnRH) neurons originate outside the CNS in the olfactory placode and migrate into the CNS, where they become integral components of the hypothalamic-pituitary-gonadal (HPG) axis. Disruption of this migration results in Kallmann syndrome (KS), which is characterized by anosmia and pubertal failure due to hypogonadotropic hypogonadism. Using candidate-gene screening, autozygosity mapping, and whole-exome sequencing in a cohort of 30 individuals with KS, we searched for genes newly associated with KS. We identified homozygous loss-of-function mutations in FEZF1 in two independent consanguineous families each with two affected siblings. The FEZF1 product is known to enable axons of olfactory receptor neurons (ORNs) to penetrate the CNS basal lamina in mice. Because a subset of axons in these tracks is the migratory pathway for GnRH neurons, in FEZF1 deficiency, GnRH neurons also fail to enter the brain. These results indicate that FEZF1 is required for establishment of the central component of the HPG axis in humans.

Brain, liver, and serum salusin-alpha and -beta alterations in Sprague-Dawley rats with or without metabolic syndrome.

BACKGROUND: This metabolic syndrome (MetS) study was designed to investigate changes in expression of the neuropeptides salusin-α (Sal-α) and salusin-ß (Sal-ß) in brain and liver tissue in response to obesity and related changes induced by high-fructose diet and explored how these changes were reflected in the circulating levels of Sal-α and Sal-b, as well as revealing how the lipid profile and concentrations of glucose and uric acid were altered. MATERIAL/METHODS: The study included 14 Sprague-Dawley rats. The control group was fed ad libitum on standard rat pellets, while the intervention group was given water with 10% fructose in addition to the standard rat pellet for 3 months. Sal-α and Sal-ß concentrations in the serum and tissue supernatants were measured by ELISA, and immunohistochemical staining was used to demonstrate expression of the hormones in brain and liver. RESULTS: Sal-α and Sal-ß levels in both the serum and the brain and liver tissue supernatants were lower in the MetS group than the control group. Sal-α and Sal-ß were shown by immunohistochemistry to be produced in the brain epithelium, the supraoptic nucleus of the hypothalamus, and the liver hepatocytes. CONCLUSIONS: The decrease in Sal-α and Sal-ß might be involved in the etiopathology of the metabolic syndrome induced by fructose.

The role of apparent diffusion coefficient values in differentiation between adrenal masses.

The aim of this study was to evaluate the utility of apparent diffusion coefficient (ADC) values in differentiation between solid adrenal masses. The ADC values of 73 adrenal lesions (54 benign, 19 malignant) in 69 patients were measured at b 100, 600 and 1000 gradients on diffusion-weighted magnetic resonance imaging (DW-MRI). No statistically significant difference was found between ADC values of benign and malignant adrenal masses, nonadenomatous benign adrenal masses and malignant adrenal masses, adrenal adenomas and nonadenomatous lesions, adenomas and metastases, adenomas and pheochromocytomas, metastases and pheochromocytomas. ADC values are not helpful in the differentiation between solid adrenal masses.

Acylated and desacylated ghrelin, preptin, leptin, and nesfatin-1 Peptide changes related to the body mass index.

This study examines the levels of acylated and desacylated ghrelin, preptin, leptin, and nesfatin-1 peptide changes related to the body mass index (BMI). The subjects were allocated to 5 groups depending on their BMIs as follows: Group I (BMI <18.5 kg/m(2)); Group II (BMI 18.5-24.9 kg/m(2)); Group III (BMI 25-29.9 kg/m(2)); Group IV (BMI 30-39.9 kg/m(2)); Group V (BMI >40 kg/m(2)). Serum acylated and desacylated ghrelin, preptin, and leptin levels were measured by the enzyme-linked immunosorbent assay (ELISA) and nesfatin-1 was measured by the enzyme immunoassay (EIA). Desacylated ghrelin levels showed a gradual and statistically significant drop from Group I to Group V, while preptin and leptin levels exhibited a gradual and significant increase from Group I to Group IV. Serum nesfatin-1 levels gradually, but not significantly, increased from Group I to Group III and showed a significant decrease in Groups IV and V. In conclusion, leptin, preptin, and acylated ghrelin (AG) levels increased with higher BMI, whereas desacylated ghrelin (DAG) decreased and nesfatin-1 showed no clear relationship to BMI.

Consequences of the Combined α-tocopherol, Ascorbic Acid and α-lipoic Acid on the Glutathione, Cholesterol and Fatty Acid Composition in Muscle and Liver of Diabetic Rats.

OBJECTIVE(S): Our objective was to evaluate the effects of a triple antioxidant combination [α-tocopherol (AT), ascorbic acid (AA) and α-lipoic acid (LA); AT+AA+LA] on the cholesterol and glutathione levels, and the fatty acid composition of liver and muscle tissues in diabetic rats. MATERIALS AND METHODS: Forty-three Wistar rats were randomly divided into five groups. The first group was used as a control. The second, third and fourth groups received STZ (45 mg/kg) in citrate buffer. The fourth and fifth groups were injected with intraperitoneal (IP) 50 mg/kg DL-AT and 50 mg /kg DL-LA four times per week and received water-soluble vitamin C (50 mg/kg) in their drinking water for a period of six weeks. RESULTS: Liver cholesterol levels in the AT+AA+LA group were lower than the control (P<0.05). Glutathione level was lower in D-2 (P<0.05) and were higher in D+AT+AA+LA and AT+AA+LA groups than the control groups (P≤ 0.05). The muscle cholesterol levels in the D-1 and D+AT+AA+LA groups were higher than the control group (P≤ 0.05). The levels of oleic acid were higher in the D-1 group and lower in the D-2 group (P<0.001). The arachidonic acid level in the D-1 and D-2 groups were lower (P<0.05), and higher in the D+AT+AA+LA group. CONCLUSION: Our results revealed that glutathione levels and the Stearoyl CoA Desaturase enzyme products in liver tissues of diabetic and non-diabetic rats were increased by triple antioxidant mixture.

Chromium modulates expressions of neuronal plasticity markers and glial fibrillary acidic proteins in hypoglycemia-induced brain injury.

AIMS: This experiment investigated if chromium (Cr) as Cr-histidinate (CrHis) and Cr29 picolinate (CrPic) have a protective role in rats with hypoglycemia-induced brain injury, assessed by neuronal plasticity and regeneration potential. MAIN METHODS: Male Sprague-Dawley rats were prospectively divided into 2 groups: control and hypoglycemic (induced by insulin administration, 15U/kg, i.p., n=56). Hypoglycemic rats were then received randomly 1) none, 2) dextrose (on the day of sampling), 3) CrHis, or 4) CrPic. Cr-chelates were delivered via drinking water (providing 8µg elemental Cr per day) for one week prior to the hypoglycemia induction. The expressions of neuroplasticity markers [neural cell adhesion molecule (NCAM), growth-associated protein-43 (GAP-43), glial fibrillary acidic protein (GFAP)], glucose transporters (GLUT), and nuclear transcription proteins [nuclear factor-kappa (NF-κB), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and 4-hydroxyl nonenal (HNE)] were determined using Western blot. KEY FINDINGS: Hypoglycemia caused increases in the expressions of GLUT-1, GLUT-3, GFAP, NF-κB and HNE and decreases in the expression of NCAM's, GAP-43 and Nrf2 in the hippocampus, cerebellum, and cortex. Cr-chelates suppressed expressions of GLUTs, GFAP, NF-κB and HNE expressions and enhanced expressions of NCAM, GAP-43 and Nrf2, which were more notable for CrHis than for CrPic. SIGNIFICANCE: In conclusion, hypoglycemia leads to cerebral injury and Cr-chelates, particularly CrHis have protective and regeneration potential in cerebral tissues through modulating neuroplasticity markers and nuclear transcription proteins as well as facilitating glucose transporters.

Primary hyperparathyroidism as an extremely rare cause of secondary myelofibrosis in childhood.

Primary hyperparathyroidism (PHP) and myelofibrosis are rare entities in childhood. Myelofibrosis secondary to PHP is also extremely rare. We report a 15-year-old boy presented with generalized weakness, vomiting, and pallor. A parathyroid adenoma was detected on the left distal parathyroid gland. PHP was diagnosed together with hepatosplenomegaly and pancytopenia. Bone marrow biopsy revealed grade 3-4 reticulin fibrosis. As early as 2 months after the left distal parathyroidectomy, hematologic parameters improved without any other intervention. His liver and spleen also gradually decreased in size. We concluded that the pancytopenia was as a result of myelofibrosis from PHP.

Examination of the tissue ghrelin expression of rats with diet-induced obesity using radioimmunoassay and immunohistochemical methods.

Currently, obesity is an important health problem in all countries, both developed and developing. Dietary habits and neurohormonal imbalances play a critical role in obesity. Circulating amounts of ghrelin, which is a neurohormonal hormone, decrease with obesity and increase with weight loss. Although it is known that both mRNA and peptide version of the ghrelin hormone are expressed in almost all tissues of both humans and animals, it is not known how obesity changes the expression of this hormone in the tissues, with the exception of the gastrointestinal system tissues. Therefore, the objective of the present study is to show how diet-induced obesity in rats changes ghrelin expression in all system tissues, and thus, to shed light on the etiopathology of obesity. The study included 12 male and 12 female 2-month-old Wistar albino species rats. The animals in the control group were fed on standard rat pellet, while those in the experiment group were fed ad libitum on a cafeteria-style diet for 2 months. When their body mass index reached 1 g/cm(2), diet-induced obese (DIO) rats were sacrificed in a sterile environment after one night fasting. Ghrelin localizations in the tissues were studied immunohistochemically using avidin-biotin-peroxidase complex (ABC) method, while tissue ghrelin amounts were analyzed using radioimmunoassay (RIA) method. When the ghrelin amounts in the urogenital system (with the exception of kidney tissues), sensory organs, respiratory system, immune system, skeletal muscle system, cardiovascular system, nervous system, and adipose tissue of rats analyzed by RIA method were compared to those in the control group, tissue ghrelin amounts in the DIO group were found lower. Immunohistochemical findings which showed a similar fall in ghrelin concentrations in the tissues were parallel to RIA results. In addition, ghrelin was shown to be synthesized in the cardiovascular system, heart muscle cells, tails of the sperms, hair follicles, lacrimal glands, tongue, and teeth of rats for the first time in this study and ghrelin syntheses in these tissues were found to decrease in obesity. Nutritional obesity is among the most common causes of obesity and the findings we have obtained through diet-induced obesity will contribute to the illumination of the etiopathology of obesity.

Pancreatic islet cell amyloidosis manifesting as a large pancreas.

A 39-year-old female patient presented to our hospital with epigastric pain lasting for two months. Laboratory results showed impaired glucose tolerance. Ultrasonography of the patient showed a hypoechoic, diffusely enlarged pancreas. CT revealed a large pancreas, with multiple calcifications. On MRI, a diffusely enlarged pancreas was seen hypointense on both T1- and T2-weighted images with heterogeneous enhancement after gadolinium administration. A biopsy of the pancreas revealed primary amyloidosis of islet cells. Decreased signal on T1-weighted images without inflammation findings on CT and MRI were clues for the diagnosis.

Diet-induced obesity suppresses ghrelin in rat gastrointestinal tract and serum.

The aims of the present study were to examine ghrelin expression in serum and gastrointestinal tract (GIT) tissues, and to measure tissue ghrelin levels and obesity-related alterations in some serum biochemical variables in rats with diet-induced obesity (DIO). The study included 12 male rats, 60 days old. The rats were randomly allocated to two groups (n = 6). Rats in the DIO group were fed a cafeteria-style diet to induce obesity, while those in the control group were fed on standard rat pellets. After a 12 week diet program including an adaptation period all rats were decapitated, tissues were individually fixed, ghrelin expression was examined by immunohistochemistry , and tissue and serum ghrelin levels were measured by radioimmunoassay. Serum biochemical variables were measured using an autoanalyzer. When the baseline and week 12 body mass index and GIT ghrelin expression were compared between DIO and control rats, BMI had increased and ghrelin expression decreased due to obesity. The RIA results were consistent with these findings. Serum glucose, LDL cholesterol, and total cholesterol levels were elevated and HDL cholesterol significantly decreased in the DIO group. A comparison of GIT tissues between the control and obese groups demonstrated that ghrelin was decreased in all tissues of the latter. This decrease was brought about a decline in the circulating ghrelin pool. This suggests that rather than being associated with a change in a single tissue, obesity is a pathological condition in which ghrelin expression is changed in all tissues.

Time-dependent changes in the serum levels of prolactin, nesfatin-1 and ghrelin as a marker of epileptic attacks young male patients.

A relationship between hormones and seizures has been reported in animals and humans. Therefore, the purpose of this study was to investigate the association between serum levels of prolactin, nesfatin-1 and ghrelin measured different times after a seizure or non-epileptic event and compared with controls. The study included a total of 70 subjects, and of whom 18 patients had secondary generalized epilepsy (SGE), 16 patients had primary generalized epilepsy (PGE), 16 patients exhibited paroxysmal event (psychogenic) and 20 healthy males were control subjects. The first sample was taken within 5min of a seizure, with further samples taken after 1, 24, and 48h so long as the patient did not exhibit further clinically observable seizures; blood samples were taken once from control subjects. Prolactin was measured immediately using TOSOH Bioscience hormone assays. Nesfatin-1 and ghrelin peptides were measured using a commercial immunoassay kit. Patients suffering from focal epilepsy with secondary generalization and primary generalized epilepsy presented with significantly higher levels of serum prolactin and nesfatin-1 and lower ghrelin levels 5min, 1 and 24h after a seizure than patients presenting with paroxysmal events (psychogenic) and control subjects; the data were similar but not statistically significant after 48h. The present study suggests that increased serum prolactin and nesfatin-1 concentrations, decreased ghrelin concentrations could be used as markers to identify patients that have suffered a recent epileptic seizure or other paroxysmal event (psychogenic).

Immunohistochemical and quantitative analysis of ghrelin in Syzygium aromaticum.

Ghrelin, an endogenous ligand of the growth hormone secretagogue receptor, has been identified in mammals, fish, amphibians, birds, reptiles and some plants. The present investigation was designed to determine whether ghrelin is present in the appetite-stimulating plants Syzygium aromaticum and Salvadora persica, using IHC (immunohistochemistry) to indicate the location of the peptide and ELISA to measure the concentration. ELISA demonstrated that a ghrelin-like substance was present at concentrations of 4070.75±664.67 and 75.25±24.49 pg/mg in the tissues of flower bud of S. aromaticum and branch of S. persica, respectively. The concentration of ghrelin in human salivary gland tissue was 436.00±95.83 pg/mg. Ghrelin was predominantly localized to the T (trachea) and PCs (parenchyma cells) in the flower bud of S. aromaticum. However, no ghrelin immunoreactivity was observed in the PC or T of the branch of S. persica. The evolutionary role of this peptide hormone in plants and animals suggests that they have evolved in a more similar way than previously thought.

Alteration in chromogranin A, obestatin and total ghrelin levels of saliva and serum in epilepsy cases.

This study was designed to measure the levels of chromogranin A (CgA), ghrelin and obestatin in serum and saliva (including CgA expression in healthy tissue) in epileptic patients to determine any significant differences between these patients and healthy controls. Samples were obtained from a total of 91 subjects: 10 newly-diagnosed primary generalized epilepsy (PGE) patients who had started treatment with valproic acid and phenytoin for seizure control; 18 PGE patients who were previously and currently receiving treatment with valproic acid and phenytoin for seizure control; 37 patients with partial epilepsy (PE) (simple, n=17 or complex, n=20) who had been and were still being treated with carbazebime for seizures; and 26 healthy controls. CgA immunoreactivity in healthy salivary gland was analyzed by immunohistochemistry and ELISA. The levels of CgA, total ghrelin and obestatin in serum and saliva were measured by ELISA. The results revealed that normal salivary gland produces its own CgA. Before treatment, CgA levels in saliva and serum were significantly greater in patients newly-diagnosed with PGE than controls. Ghrelin and CgA concentrations were also greater in PGE patients previously or currently treated with drugs, and in patients with simple or complex partial epilepsy (PE) previously or currently treated with drugs, than in healthy normal controls. In conclusion, salivary concentrations of CgA, ghrelin and obestatin were similar to their serum levels, so saliva might be a desirable alternative to serum for measuring these hormones because it is easy and painless to collect.