Non-pharmaceutical interventions to reduce COVID-19 transmission in the UK: a rapid mapping review and interactive evidence gap map.

BACKGROUND: Non-pharmaceutical interventions (NPIs) were crucial in the response to the COVID-19 pandemic, although uncertainties about their effectiveness remain. This work aimed to better understand the evidence generated during the pandemic on the effectiveness of NPIs implemented in the UK. METHODS: We conducted a rapid mapping review (search date: 1 March 2023) to identify primary studies reporting on the effectiveness of NPIs to reduce COVID-19 transmission. Included studies were displayed in an interactive evidence gap map. RESULTS: After removal of duplicates, 11 752 records were screened. Of these, 151 were included, including 100 modelling studies but only 2 randomized controlled trials and 10 longitudinal observational studies.Most studies reported on NPIs to identify and isolate those who are or may become infectious, and on NPIs to reduce the number of contacts. There was an evidence gap for hand and respiratory hygiene, ventilation and cleaning. CONCLUSIONS: Our findings show that despite the large number of studies published, there is still a lack of robust evaluations of the NPIs implemented in the UK. There is a need to build evaluation into the design and implementation of public health interventions and policies from the start of any future pandemic or other public health emergency.

Analysis of outcomes of emergency general and gastrointestinal surgery during the COVID-19 pandemic.

BACKGROUND: Few surgical studies have provided adjusted comparative postoperative outcome data among contemporary patients with and without COVID-19 infection and patients treated before the pandemic. The aim of this study was to determine the impact of performing emergency surgery in patients with concomitant COVID-19 infection. METHODS: Patients who underwent emergency general and gastrointestinal surgery from March to June 2020, and from March to June 2019 in 25 Spanish hospitals were included in a retrospective study (COVID-CIR). The main outcome was 30-day mortality. Secondary outcomes included postoperative complications and failure to rescue (mortality among patients who developed complications). Propensity score-matched comparisons were performed between patients who were positive and those who were negative for COVID-19; and between COVID-19-negative cohorts before and during the pandemic. RESULTS: Some 5307 patients were included in the study (183 COVID-19-positive and 2132 COVID-19-negative during pandemic; 2992 treated before pandemic). During the pandemic, patients with COVID-19 infection had greater 30-day mortality than those without (12.6 versus 4.6 per cent), but this difference was not statistically significant after propensity score matching (odds ratio (OR) 1.58, 95 per cent c.i. 0.88 to 2.74). Those positive for COVID-19 had more complications (41.5 versus 23.9 per cent; OR 1.61, 1.11 to 2.33) and a higher likelihood of failure to rescue (30.3 versus 19.3 per cent; OR 1.10, 0.57 to 2.12). Patients who were negative for COVID-19 during the pandemic had similar rates of 30-day mortality (4.6 versus 3.2 per cent; OR 1.35, 0.98 to 1.86) and complications (23.9 versus 25.2 per cent; OR 0.89, 0.77 to 1.02), but a greater likelihood of failure to rescue (19.3 versus 12.9 per cent; OR 1.56, 95 per cent 1.10 to 2.19) than prepandemic controls. CONCLUSION: Patients with COVID-19 infection undergoing emergency general and gastrointestinal surgery had worse postoperative outcomes than contemporary patients without COVID-19. COVID-19-negative patients operated on during the COVID-19 pandemic had a likelihood of greater failure-to-rescue than prepandemic controls.

Impact of severe hematological abnormalities in the outcome of hospitalized patients with influenza virus infection.

Although hematological abnormalities have been described among patients with influenza virus infection, little is known about their impact on the outcome of the patients. The aim of this study was to assess the frequency and clinical impact of severe hematological abnormalities in patients with confirmed influenza virus infection. This was an observational retrospective study including all adult patients with diagnosis of influenza virus infection hospitalized from January to May 2016 in our institution. Influenza virus infection was diagnosed by means of rRT-PCR assay performed on respiratory samples. Poor outcome was defined as a composite endpoint in which at least one of the following criteria had to be fulfilled: (a) respiratory failure, (b) SOFA ≥2, or (c) death. Two hundred thirty-nine patients were included. Applying the HLH-04 criteria for the diagnosis of hemophagocytic syndrome, cytopenias (hemoglobin ≤9 g/dl, platelets <100,000/µl or neutrophils <1,000/µl) were present in 51 patients (21%). Patients with hematological abnormalities showed higher SOFA scores, respiratory failure, septic shock and in-hospital mortality than the remaining patients. The composite endpoint was present in 33.3% in the cytopenias group vs. 13.3% in the group without cytopenias (p=0.001). In a multivariate analysis, variables associated with the composite endpoint were: use of steroids prior to present admission (OR: 0.12; 95% CI: 0.015-0.96, p=0.046), presence of any hematological abnormality (OR: 3.54; 95% CI:1.66-7.51, p= 0.001), and LDH>225 U/l (OR:4.45; CI:1-19.71, p=0.049). Hematological abnormalities are not uncommon among hospitalized patients with influenza virus infection, and they are associated with a poorer outcome.

Hypogonadism in aged hospitalized male patients: prevalence and clinical outcome.

OBJECTIVE: Male hypogonadism is common in the elderly and has been associated with increased risk of mortality. Our objective has been to assess the prevalence of primary and central hypogonadism in elderly male patients admitted to the hospital because of acute illness. We also evaluated the relationships between gonadal dysfunction and in-hospital mortality. PATIENTS AND METHODS: 150 patients, aged ≥65 years, admitted during 2010 and 2011 in our geriatric unit, were studied. Serum concentrations total, bioavailable and free testosterone, as well as of follicle-stimulating hormone and luteinizing hormone were quantified in every patient. Hypogonadism was defined by the presence of serum testosterone levels lower than 200 ng/dl. RESULTS: Hypogonadism was found in 80 patients (53.3 %). Serum gonadotropin concentrations were elevated in 43.7 % of these patients, whereas 41.3 % of hypogonadic patients showed normal and 15 % low gonadotropin concentrations. Respiratory tract infection and congestive heart failure were the main causes of hospitalization in hypogonadal men, whereas acute cerebrovascular disease was the main reason for admission in eugonadal patients. Of the 13 patients who died during hospitalization, 12 were hypogonadic. Patients who died showed significantly lower serum levels of total, free and bioavailable testosterone than those found in patients who survived. CONCLUSION: Our results show that about half of patients admitted for acute illness have hypogonadism, mainly of non-hypergonadotropic type. Gonadal hypofunction is significantly related with in-hospital mortality. A low value of serum testosterone may be a predictor for mortality in elderly male patients.

Readmission Rates Among Acute Reperfusion Treatment Modalities for Patients With Ischemic Stroke.

Background and purpose: Understanding various aspects associated with readmission after acute ischemic stroke (AIS) is an important priority. Our study aims to examine whether 60-day readmission rates differed among patients with AIS who were treated with different acute reperfusion treatment modalities along with associated clinical factors. Methods: This is a retrospective analysis of a continuous cohort of patient with AIS, who received either intravenous recombinant tissue plasminogen activator (IV rtPA), endovascular treatment (EVT) or both, and were discharged alive. Patients readmitted within 60 days were identified as the readmission group. Multivariable logistic regression was used to identify all-cause readmission post-stroke between treatment groups. Results: The final cohort comprised of 358 patients with AIS receiving IV rtPA only (N = 160), EVT only (N = 106), or both (N = 92). Fifty-six patients were readmitted to the hospital within 60-day follow-up period. The adjusted logistic regression model indicated that compared to patients who received IV tPA only, patients receiving both IV rtPA and EVT had significantly lower odds (OR = .27; 95% CI = .10, .75)) of getting readmitted within 60-day post-discharge from stroke admission. Conclusion: In this sample of AIS hospitalizations, treatment-type was positively associated with 60-day readmission. Future studies are necessary to understand whether treatment-related adverse events, and readmission are avoidable.

Impact of aromatic residues on the intrinsic disorder and transitional behaviour of model IDPs.

Understanding the interplay between order and disorder in intrinsically disorder proteins (IDPs), and its impact on the properties and features of materials manufactured from them, is a major challenge in the design of protein-based synthetic polymers intended for advanced functions. In this paper an elastin-like diblock co-recombinamer amphiphile (Phe-ELR) based on a hydrophobic block containing five phenylalanine (Phe) residues proximal to the carboxyl function of a glutamic acid (Glu) residue upon folding, and with Glu as the guest residue in the hydrophilic part, was engineered and its assembly behaviour compared with another amphiphilic ELR used as control. Phe-ELR was tailored in order to clarify the impact of the presence of aromatic residues in the amino acid sequence, which even in early studies by Urry's group already demonstrated a certain out-of-trend behaviour compared with other apolar amino acids, especially non-aromatic ones, on ELR behaviour. The combination of several experimental techniques indicates strong molecular interactions associated with the Phe residue, thus resulting in limited reversible character of the temperature-induced transitions during sequential thermal cycles, a lower than expected transition enthalpy, and clear differences in its supramolecular assembly with respect to the control ELR. A distinctive pre-aggregated state for the Phe-ELR under any condition of pH and temperature is found. Eventually, this state gives rise to Phe-core micelles or a solid jelly-like material, depending on the concentration, pH and presence of salts. In conclusion, it appears that the presence of aromatic residues and their ability to promote strong inter- and intramolecular interactions at any temperature and pH causes a complete modification of the order-disorder interplay present in other, non-aromatic ELRs. These molecular events have a profound impact on the physical properties of the resulting polymer when compared with other ELRs. This work helps to shed light on the limits that govern intrinsic disorder in ELRs beyond its inverse temperature transition.

Severe hyperthyroidism: aetiology, clinical features and treatment outcome.

BACKGROUND: Severe hyperthyroidism (SH) is a serious medical disorder that can compromise life. There have not been systematic studies in which SH has been evaluated in detail. Here, our aims were: (1) to analyse both clinical and analytical features and outcome in patients with SH and (2) to compare these data with those found in more usual forms of hyperthyroidism. Patients and methods All patients diagnosed of SH (free thyroxine, FT4 > 100 pmol/l, NR: 11-23) seen in our endocrinology clinic in the last 15 years were studied and compared with a sample of patients with mild (mH; FT4, 23-50 pmol/l) and moderate (MH; FT4, 51-100 pmol/l) hyperthyroidism. Aetiology, clinical analytical and imaging data at diagnosis, therapeutic response and outcome were registered. Results A total of 107 patients with overt hyperthyroidism (81 females, mean age +/- SD 46.9 +/- 16.1 years) were evaluated. We studied a historic group with SH (n = 21; 14 females, 40.9 +/- 17.2 years) and, as a comparator group, we analyszed the data of 86 hyperthyroid patients (67 females, 48.4 +/- 15.5.6 years, NS) comparable in age and gender. The comparator group was classified in MH (n = 37, 26 females, 47.2 +/- 16.6 years) and mH (n = 49, 41 females, 49.4 +/- 14.8 years). In comparison with mH group, SH patients were significantly (P < 0.05) younger and showed a greater proportion of first episode of thyroid hyperfunction (P < 0.05). Graves' disease was the main aetiology in the three groups, but patients with SH showed the highest titre of TSH-receptor antibodies (TRAb) (P < 0.001). Heart rate and size of goitre were higher in SH group than in mH and MH groups (P < 0.01). Atrial fibrillation was more frequently reported in SH group than in MH and mH groups (15.8%vs. 5.4% and 0%, respectively, P < 0.05). RESULTS: from logistic regression analysis showed that younger age [OR 0.958 (95% CI, 0.923-0.995), P = 0.026], presence of asthenia [OR 4.35 (1.48-12.78), P = 0.008] and higher heart rate [OR 1.03 (1.01-1.06), P = 0.013] were independent clinical variables associated to SH. SH patients showed similar biochemical parameters in comparison with mH group, except for increased serum aspartate aminotransferase (AST) (P < 0.01) and calcium (P < 0.05) levels, and decreased serum cholesterol (P < 0.05) and albumin (P < 0.05) concentrations. Logistic regression analysis showed that only AST [OR 1.07 (1.02-1.11), P = 0.005] was an independent biochemical variable associated to SH. No differences in the type of therapy, cure rate and time in achieving cure were found in SH subjects in relation to patients with milder forms of hyperthyroidism. FT4 was the only independent predictor of cure [OR 0.98 (CI 95%, 0.97-0.99), P < 0.05]. CONCLUSIONS: Graves' disease is the most common aetiology in patients with SH. This type of hyperthyroidism is usually de novo and is accompanied by more clinical signs, symptoms, and analytical derangements, as well as higher titres of TRAb at diagnosis than milder forms of hyperthyroidism. The present data are not able to show differences in treatment modality, time to achieve cure, and remission rate among patients with mild, moderate and severe hyperthyroidism.

Serum thyrotropin concentration is an early marker of normalization of low triiodothyronine syndrome in aged hospitalized patients after discharge.

OBJECTIVES: To assess short-term spontaneous evolution of alterations in thyroid function tests in aged hospitalized patients after discharge. METHODS: A group of 146 patients (mean age±SD 85.9±6.2 yr) was studied. Serum concentrations of TSH, free T4 (FT4), and free T3 (FT3) were evaluated in every patient both after admission and 1 month after discharge. RESULTS: At entry, both serum TSH [median (interquartile range), 2.19mU/l (0.89-2.31)] and FT4 (mean±SD, 16.7±3.4 pmol/l) concentrations were into the normal range, whereas serum FT3 concentrations were low (3.3±0.7 pmol/l). After discharge TSH and FT4 concentrations remained normal and FT3 low. However, both serum TSH [2.53 mU/l (1.24-3.33); p<0.01] and FT3 (3.7±1.0 pmol/l; p<0.001) concentrations significantly increased. Most patients (no.=124, 84.9%) showed the euthyroid sick syndrome (ESS). After discharge, ESS diminished to 76 (52.1%) subjects. Patients who normalized thyroid function tests showed significantly lower TSH values at entry compared with those who persisted with altered thyroid function tests [1.27 mU/l (0.69-1.89) vs 1.69mU/l (0.96-2.91), p<0.05]. Logistic regression analysis showed that serum levels of TSH at admission was the only variable negatively related to normalization of thyroid function [odds ratio 0.730; confidence interval 95%, 0.567-0.940; p=0.01). CONCLUSIONS: About 35%of aged patients hospitalized for acute illness spontaneously normalize their thyroid function tests 1 month after discharge, mainly due to the correction of ESS. Serum TSH levels at admission seem to be the only variable negatively related to normalization of thyroid function at this time.

Self-assembly in elastin-like recombinamers: a mechanism to mimic natural complexity.

The topic of self-assembled structures based on elastin-like recombinamers (ELRs, i.e., elastin-like polymers recombinantly bio-produced) has released a noticeable amount of references in the last few years. Most of them are intended for biomedical applications. In this review, a complete revision of the bibliography is carried out. Initially, the self-assembly (SA) concept is considered from a general point of view, and then ELRs are described and characterized based on their intrinsic disorder. A classification of the different self-assembled ELR-based structures is proposed based on their morphologies, paying special attention to their tentative modeling. The impact of the mechanism of SA on these biomaterials is analyzed. Finally, the implications of ELR SA in biological systems are considered.

A GHEP-ISFG collaborative study on the genetic variation of 38 autosomal indels for human identification in different continental populations.

A collaborative effort was carried out by the Spanish and Portuguese Speaking Working Group of the International Society for Forensic Genetics (GHEP-ISFG) to promote knowledge exchange between associate laboratories interested in the implementation of indel-based methodologies and build allele frequency databases of 38 indels for forensic applications. These databases include populations from different countries that are relevant for identification and kinship investigations undertaken by the participating laboratories. Before compiling population data, participants were asked to type the 38 indels in blind samples from annual GHEP-ISFG proficiency tests, using an amplification protocol previously described. Only laboratories that reported correct results contributed with population data to this study. A total of 5839 samples were genotyped from 45 different populations from Africa, America, East Asia, Europe and Middle East. Population differentiation analysis showed significant differences between most populations studied from Africa and America, as well as between two Asian populations from China and East Timor. Low FST values were detected among most European populations. Overall diversities and parameters of forensic efficiency were high in populations from all continents.

Thyrotropin-releasing hormone stimulation of adrenocorticotropin production by mouse pituitary tumor cells in culture: possible model for anomalous release of adrenocorticotropin by thyrotropin-releasing hormone in some patients with Cushing's disease and Nelson's syndrome.

ACTH-producing mouse pituitary tumor cells in culture (AtT-20/NYU-1 cells) were found to have binding sites for thyrotropin-releasing hormone (TRH). These putative receptors bound TRH with high affinity; the apparent equilibrium dissociation constant was 3.7 nM. The affinity of the receptors for a series of TRH analogues was similar to those previously reported for TRH-receptor interactions on thyrotropic and mammotropic cells in culture. Like some human pituitary tumors in situ, AtT-20/NYU-1 cells were found to produce the alpha subunit of the glycoprotein hormones (alpha). Alpha accumulation in the medium was constant (3.1 ng/mg cell protein per h) and was not affected by TRH. In contrast, TRH increased the amount of ACTH accumulated in the medium from AtT-20/NYU-1 cells to 190 and 420% of control at 1 and 24 h, respectively. TRH induced a dose-dependent increase in ACTH release during a 30-min incubation; half-maximal stimulation occurred at approximately 0.1 nM. TRH had no effect on ACTH release in vitro from anterior pituitary cells derived from normal rats. Because TRH stimulates release of ACTH in some untreated patients with Cushing's disease and Nelson's syndrome as well as pathological states associated with pituitary tumors (but not in normal subjects), AtT-20/NYU-1 cells may serve as an important in vitro model for human pituitary ACTH-secreting adenomas. Moreover, these findings suggest that the primary abnormality in Cushing's disease and Nelson's syndrome, allowing TRH stimulation of ACTH release, may be intrinsic to neoplastic adrenocorticotrophs rather than in neuroregulation of ACTH release.

Hypogonadism and Mortality in Aged Hospitalized Male Patients: A 5-Year Prospective Observational Study.

OBJECTIVE: To investigate the relationship between hypogonadism and mortality in aged hospitalized male patients. DESIGN: A 5-year prospective observational study was conducted. Gonadal function was assessed at hospital admission and mortality was registered in the follow-up period. PATIENTS AND METHODS: We studied all patients≥65 years admitted for any reason during 2010 and 2011. Serum T concentrations were quantified in all patients. Hypogonadism was defined by the presence of serum T levels<200 ng/dl. Number of deaths and all-cause and cardiovascular (CV) mortality were registered until December 31(st), 2014. RESULTS: During the study 150 patients were admitted and 103 (68.7%) of them died during follow-up. Hypogonadism was positively associated with mortality (P=0.036). The percentage of hypogonadal patients was significantly (P=0.02) higher in the group of patients who died in hospital compared with those who died after hospital discharge and those who survived. CV disease was the main cause of death in 52 patients (50.5%). Kaplan-Meier analysis showed a median survival time for all-cause mortality of 2.0 (0-16.5) months and 21.0 (5.0-33.2) months for patients with and without hypogonadism, respectively (P<0.001). Similar findings were found when analyzing mortality due to CV disease (P=0.009). Hypogonadism was a strong independent predictor for all-cause (adjusted multivariate analysis, HR 3.35; 1.55-7.23, P=0.002) and CV mortality (HR 2.14; 1.18-3.86, P=0.012). CONCLUSIONS: Hypogonadism discovered during hospitalization is associated with in-hospital and long-term mortality in elderly male patients and predicts both all-cause mortality and CV mortality in this population.

Natural course of hypogonadism diagnosed during hospitalization in aged male patients.

Our aim was to assess short-term natural course of hypogonadism diagnosed during hospitalization for acute disease in aged male patients after discharge. A group of 43 hypogonadal males, aged 86.7±5.7 year, was studied. Serum concentrations of testosterone (T) and gonadotropins (follicle-stimulating hormone, FSH, and luteinizing hormone, LH) were measured in every patient both at admission and one month after discharge. Mean serum T at entry was 115.4±48.0 ng/dl. Hypogonadism was hyper-, hypo-, and normogonadotropic in 20 (46.5%), 20 (46.5%), and 3 (7.0%) patients, respectively. One month after discharge serum T concentrations increased significantly (230.9±135.6 ng/dl, p<0.001). At this point, more than half of the patients (n=27, 62.8%) showed normal serum T concentrations. Both gonadotropins, FSH (p<0.001), and LH (p=0.04) also increased one month after discharge. Approximately, half of the patients (13, 48.1%) who normalized serum T concentrations also showed normal serum gonadotropin concentrations. Patients who normalized their serum T concentrations one month after discharge showed significantly higher baseline values of T (134.7±33.9 ng/dl) than those who persisted with hypogonadism (n=16, 32.7%; 82.8±51.6 ng/dl, p<0.001). Lastly, serum T was the only independent predictor for achieving eugonadal status (OR 1.030; CI 95%, 1.010-1.050; p<0.001). In conclusion, about 63% of aged patients hospitalized for acute illness with hypogonadism discovered during hospitalization spontaneously normalize their serum T concentrations one month after discharge. Serum gonadotropin concentrations also increased after discharge. Serum T levels at admission was an independent predictor for the normalization of serum T concentrations.

Thyrotropin-releasing hormone (TRH) action in mouse thyrotropic tumor cells in culture: evidence against a role for adenosine 3',5'-monophosphate as a mediator of TRH-stimulated thyrotropin release.

It has been suggested that TRH stimulation of TSH release is mediated by the adenylate cyclase-cAMP system. To determine whether cAMP is a necessary intracellular messenger for TRH stimulation of TSH release, we have performed detailed studies of the TRH effect employing a nearly homogeneous population of mouse thyrotropic tumor cells in culture. Dibutyryl cAMP, methylisobutylxanthine, and cholera toxin caused an increase in TSH release which was additive to that of TRH. TRH stimulated TSH release in a dose-dependent fashion; half-maximal stimulation occurred at approximately 0.6 nM but had no effect on total intracellular cAMP levels measured in the presence or absence of methylisobutylxanthine. There was no correlation between total intracellular cAMP levels and TSH release after 1 h. Moreover, there was no effect of TRH on protein kinase-bound or total intracellular cAMP levels at 1, 5, or 60 min of incubation. Lastly, TRH had no effect on adenylate cyclase activity in homogenates of thyrotropic cells in the presence or absence of guanylylimidodiphosphate. These results suggest that stimulation of TRH release by TRH from these cells does not involve cAMP as an intracellular messenger.

Primary structure and synthesis of Imperatoxin A (IpTx(a)), a peptide activator of Ca2+ release channels/ryanodine receptors.

We present the complete amino acid sequence of Imperatoxin A (IpTx(a)), a 33-amino-acid peptide from the venom of the scorpion P. imperator which activates Ca2+ release channels/ryanodine receptors (RyR) of sarcoplasmic reticulum (SR). The amino acid sequence of IpTx(a) shows no homology to any scorpion toxin so far described, but shares some homology to the amino acid sequence of Tx2-9 and agelenin, two spider toxins that target neuronal P-type Ca2+ channels. We also describe the total synthesis of IpTx(a) and demonstrate that it efficiently activates RyRs with potency and affinity identical to those of native IpTx(a). The use of synthetic IpTx(a) should help in the identification of the structural motifs of RyR critical for channel gating.

Effect of prenatal uterine position on male and female rats sexual behavior.

It is well known that female rats developing close to a male in utero show a higher frequency of heterotypical or male-like behavior in adulthood, and have longer anogenital distances. The present investigation was designed to evaluate the in utero masculine influence on the homotypical sexual behavior of male and female rats. Also explored was the influence on body weight on Gestation Day 21 (day of cesarean delivery) and 21, 40. and 120 days after birth, testicle weight following the gonadectomy of males on Day 40, and serum testosterone in males and females on the day of delivery. The presence of a contiguous male fetus located caudally with respect to uterine blood flow led to the masculinization of male-like behavior in male rats, the defeminization of female like behavior in females and to increased body weights on Day 21 of gestation in both sexes. No significant differences were detected in the remaining parameters. Findings indicated a gradation in the intensity of expression of male and female sexual behavior in adulthood related to the intrauterine position resulting in interindividual variability. The possible implication of this physiological phenomenon in the structure of rodent populations is discussed.

Cannabinoid effects on anxiety-related behaviours and hypothalamic neurotransmitters.

The aim of the present study was to examine the effects of the cannabinoid agonist CP 55,940 and the antagonist SR 141716A, alone and in combination, on rat exploratory and anxiety-like behaviour in the holeboard and elevated plus-maze tests. A further aim was to evaluate the effects of these treatments on hypothalamic neurotransmitters. Animals treated with CP 55,940 doses of 0.125 and 0.1 mg/kg exhibited less exploration and an increase in anxiety-like behaviour accompanied by great motor inhibition. No hypoactivity was seen at 0.075 mg/kg dosage, but anxiety and neophobic responses persisted, indicating independent and specific effects. Motor activity effects induced by CP 55,940 were reversed by pretreatment with SR 141716A (3 mg/kg). Surprisingly, when administered on its own, the antagonist also induced a reduction in exploratory parameters and an increase in anxiety-like responses. These apparently similar effects might be caused by different neural mechanisms. Finally, CP 55,940 increased hypothalamic dopamine and serotonin levels. These increases might be involved in the activation of the hypothalamic-pituitary-adrenal axis described for cannabinoids.

Tissue-engineered nipple reconstruction.

We describe a simple, effective approach to the creation of autologous tissue-engineered cartilage in the shape of a human nipple by injecting a reverse thermosensitive polymer seeded with autologous chondrocytes in an immunocompetent porcine animal model. A biodegradable, biocompatible copolymer of polyethylene oxide and polypropylene oxide (Pluronic F-127), which exists as a liquid below 4 degrees C and polymerizes to a thick gel when it is exposed to physiologic temperatures (body temperatures), was used as a vehicle for chondrocyte delivery and as a scaffold to guide growth. Autologous chondrocytes isolated from porcine auricular elastic cartilage and suspended in 30% (weight/volume) Pluronic F-127 were injected on the ventral surface of the pigs from which the cells had been isolated. A circumferential subdermal suture was used to support the contour of the implant and assist in its projection in the form of a human nipple. After 3 weeks, the skin over and surrounding the implant was tattooed to create the appearance of a human nipple-areolar complex. As controls, an equal number of injections were made using either cells alone (not suspended in hydrogel), or hydrogel alone. After 10 weeks, all specimens were excised and examined both grossly and histologically. Before harvesting, visual inspection of the tattooed chondrocyte-Pluronic F-127 hydrogel implant sites revealed that they closely resembled a human female nipple-areolar complex. Nodules were similar in size, shape, and texture to a human nipple at each injection site. Glistening opalescent tissue was surgically isolated from each implant site. Hematoxylin and eosin, safranine o, trichrome blue, and Verhoeff's stains of the experimental implants showed nodules with the characteristic histologic signs of elastic cartilage. Control injections of copolymer hydrogel alone exhibited no evidence of cartilage formation. Control injections of chondrocytes alone showed evidence of dissociated microscopic nodules of elastic cartilage.

The effects of acute treatment with delta9-THC on exploratory behaviour and memory in the rat.

The aim of the present study was to evaluate the effects of delta9-tetrahydrocannabinol (delta9-THC) on exploratory behaviour and memory, independent of its locomotor suppressive effects. Dopamine (DA) and noradrenaline (NA) contents were determined in the areas of the brain directly related to such behaviours (hippocampus, striatum and amygdala). An acute dose of delta9-THC led to a decrease in exploratory parameters and motor activity during the holeboard test. The radial arm maze was used to evaluate the effects of this cannabinoid substance on memory. Animals treated with delta9-THC committed more errors in the maze test compared to control, particularly when the retention process was put to test. Furthermore, treatment with delta9-THC led to reduced NA contents in the hippocampus and increased DA contents in the amygdala, without changes in the striatum.