Group B Streptococcus Meningitis in an Adult Woman with Type 2 Diabetes and Ethmoid Roof Defect. Impact on "frontal" Cognitive Functions.

Background: Community-acquired bacterial meningitis in adults represents one of the most severe infectious diseases worldwide with potentially life-threatening medical complications. Several infectious agents can cause acute meningitis. Although group B Streptococcus is more prevalent in newborns, infection can also lead to meningitis in older adults, particularly those with underlying health issues. Case Description: A 53-year-old woman with a body mass index of 28.7 kg/m2, type 2 diabetes mellitus, and dyslipidaemia presented to the emergency department of Santa Maria della Stella Hospital (Orvieto, Italy) with confusion, low-grade fever, echolalia, and hyperglycaemia. Computed tomography scans of the brain revealed a hypodensity in the left anterior frontal lobe and an osteodural defect of the rhinobase. Meningitis was suspected and empiric broad-spectrum antibiotic therapy with corticosteroids and insulin were administered while the results of the cerebrospinal fluid analysis confirmed the diagnosis of group B Streptococcus meningitis. Repeat imaging at 48 hours revealed enlargement of the hypodense lesion. The frontal assessment battery indicated deficits in executive functions. Prompt treatment led to rapid clinical improvement. Following the restoration of euglycemic status and hemodynamic stabilization, a follow-up magnetic resonance imaging confirmed the ischaemic lesion and showed cerebrospinal fluid in the sella turcica. The patient was then transferred to neurorehabilitation. Conclusions: The complex interactions among multiple risk factors resulted in an atypical clinical case of group B Streptococcus meningitis, which was promptly treated with empiric antibiotic therapy to mitigate neurocognitive deficits. LEARNING POINTS: Group B Streptococcus can cause meningitis in adults with poorly controlled type 2 diabetes mellitus and should be promptly treated with empiric broad-spectrum antibiotics.An osteodural defect of the ethmoid roof together with idiopathic intracranial hypertension may result in empty sella turcica and CSF rhinorrhoea, promoting the dissemination of the pathogen.Meningitis patients with pre-existing diabetic cerebral vasculopathy may develop cerebrovascular complications and cognitive impairments.

A pro-diabetogenic mtDNA polymorphism in the mitochondrial-derived peptide, MOTS-c.

Type 2 Diabetes (T2D) is an emerging public health problem in Asia. Although ethnic specific mtDNA polymorphisms have been shown to contribute to T2D risk, the functional effects of the mtDNA polymorphisms and the therapeutic potential of mitochondrial-derived peptides at the mtDNA polymorphisms are underexplored. Here, we showed an Asian-specific mitochondrial DNA variation m.1382A>C (rs111033358) leads to a K14Q amino acid replacement in MOTS-c, an insulin sensitizing mitochondrial-derived peptide. Meta-analysis of three cohorts (n = 27,527, J-MICC, MEC, and TMM) show that males but not females with the C-allele exhibit a higher prevalence of T2D. In J-MICC, only males with the C-allele in the lowest tertile of physical activity increased their prevalence of T2D, demonstrating a kinesio-genomic interaction. High-fat fed, male mice injected with MOTS-c showed reduced weight and improved glucose tolerance, but not K14Q-MOTS-c treated mice. Like the human data, female mice were unaffected. Mechanistically, K14Q-MOTS-c leads to diminished insulin-sensitization in vitro. Thus, the m.1382A>C polymorphism is associated with susceptibility to T2D in men, possibly interacting with exercise, and contributing to the risk of T2D in sedentary males by reducing the activity of MOTS-c.

Adherence to Mediterranean diet moderates the association between multimorbidity and depressive symptoms in older adults.

AIM: Adherence to Mediterranean Diet (Med-Diet) has been associated with a lower incidence of chronic diseases and may be associated with lower risk for depression. The aim of the present study was to investigate (i) the association of adherence to Med-Diet with depressive symptoms and multimorbidity in a cohort of geriatric medical outpatients, and (ii) the role of Med-Diet in mediating the association between depressive symptoms and multimorbidity. METHODS: A total of 143 geriatric patients (mean age: 73.1 ± 8.35) were included. Adherence to Med-Diet was evaluated using a validated 14-item questionnaire; depressive and cognitive symptoms were assessed through the 15-item Geriatric Depression Scale (GDS) and Mini Mental State Examination (MMSE) respectively; multimorbidity was evaluated using the Cumulative Illness Rating Scale for Geriatrics (CIRSG-SI). RESULTS: Significant associations were found between MDQ score, GDS and CIRSG-SI (MDQ score and GDS: r= -0.206, p = 0.014; MDQ score and CIRSG-SI: r= -0.247, p = 0.003; GDS and CIRSG-SI: r = 0.251; p = 0.003). These associations remained significant after adjusting for potential confounding factors. A mediational model analysis showed that the direct effect of CIRSG-SI on GDS was significant (b = 1.330; se = 0.59; p = 0.028) with this effect being counterbalanced by higher MDQ scores (indirect effect of CIRS-G on GDS through MDQ: b = 0.382; se = 0.19; p = 0.048). CONCLUSION: These findings (i) add to the accumulating evidence that Med-Diet may have a positive impact on mental health in the elderly, and (ii) suggest that Med-Diet may contribute, at least in part, to protect geriatric patients with multimorbidity from the development of depressive symptoms, ultimately promoting healthy aging.

The relationship between Vitamin D and depressive disorders.

Studies have suggested a relationship between low circulating levels of Vitamin D and depression. Vitamin D deficiency may be a consequence of depression-related factors, such as reduced sun exposure, decreased outdoor activity, and dietary changes, but it can also play a role in the pathophysiology of depressive conditions through a range of molecular mechanisms. In the present manuscript, findings related to prospective longitudinal studies on the relationship between Vitamin D levels and depressive symptoms and to randomized controlled trials on Vitamin D supplementation for depressive disorders are reviewed.

Thyroid hormone regulates fibronectin expression through the activation of the hypoxia inducible factor 1.

Thyroid hormones regulate gene expression via both canonical and non-canonical signaling. Hyperthyroidism is associated with elevated plasma levels of fibronectin (FN): in this study we elucidate the molecular mechanism through which triiodothyronine (T3) regulates FN and demonstrate that T3 induces FN expression via a non-canonical pathway by activating hypoxia-inducible factor-1 (HIF-1). We found that T3 treatment increased cellular and secreted FN in human hepatoma cells (HepG2) and human dermal fibroblasts (HF) via the PI3K/Akt/HIF-1 pathway. The inhibition of either Akt phosphorylation with wortmannin or HIF-1 with YC1 in both cell types prevented HIF-1α synthesis and FN positive regulation upon T3 treatment. We showed that HIF-1α overexpression per se was sufficient to up-regulate FN in both cell lines as demonstrated by the transient transfection of both the constitutively active and wild-type forms of HIF-1α. Our data demonstrate the involvement of the PI3K/Akt/HIF-1 pathway in mediating T3 induced FN up-regulation.

Spleen dimensions are inversely associated with lysosomal acid lipase activity in patients with non-alcoholic fatty liver disease.

Fatty liver and splenomegaly are typical features of genetic lysosomal acid lipase (LAL) deficiency. No data in adult patients with non-genetic reduction of LAL activity are available. We investigate the association between spleen dimensions and LAL activity in non-alcoholic fatty liver disease (NAFLD) patients, in whom a reduced LAL activity has been reported. We include 425 consecutive patients who underwent abdominal ultrasound to evaluate hepatic steatosis and spleen dimensions. LAL activity was measured with dried blood spot method (Lalistat2). NAFLD was present in 74.1% of screened patients. Higher median spleen longitudinal diameter (10.6 vs. 9.9 cm; p < 0.001) and spleen area (SA) (32.7 vs. 27.7 cm2; p < 0.001), together with a higher and proportion of splenomegaly (17.8 vs. 5.5%, p = 0.001), are present in patients with NAFLD compared to those without. In NAFLD patients, median LAL activity is 0.9 nmol/spot/h. LAL activity is lower in 56 patients with splenomegaly, as compared to those without (p = 0.009). At multivariable logistic regression analysis, age (above median, OR 0.344; p = 0.003), LAL activity (below median, OR 2.206, p = 0.028), and platelets (OR 0.101, p = 0.002) are significantly associated with splenomegaly. NAFLD patients disclose a relatively high prevalence of spleen enlargement and splenomegaly, which are significantly associated with a reduced LAL activity, suggesting that LAL may contribute to spleen enlargement in this setting.

Psychoeducational intervention focused on healthy living improves psychopathological severity and lifestyle quality in psychiatric patients: preliminary findings from a controlled study.

BACKGROUND: Individuals with psychiatric disorders incur an increased risk of morbidity and mortality, with higher prevalence of cardio-metabolic risk factors s largely contributing to a significant reduction in life expectancy. OBJECTIVES: The aim of the present study was at evaluating the clinical effectiveness of an educational intervention targeting lifestyle habits in patients with mood and psychotic disorders. METHODS: Patients (n = 32) were randomly assigned to receive, in addition to the pharmacological treatment, either five sessions of group psychoeducation focused on healthy lifestyle or five sessions of a control group therapy. RESULTS: Both psychopathological severity (i.e. the brief psychiatric rating scale) and lifestyle quality (i.e. physical activity, sleep quality and adherence to the Mediterranean diet) improved significantly over time in patients who underwent specific psychoeducational sessions but not in the controls. CONCLUSIONS: These findings add to the accumulating evidence that educational interventions focused on lifestyle habits can ameliorate general and mental health in patients with psychiatric disorders and suggest that educational programs represent an effective non-pharmacological intervention to manage drug-induced cardiometabolic disturbances.

Cannabis: a self-medication drug for weight management? The never ending story.

In a society highly focused on physical appearance, people are increasingly using the so-called performance and image-enhancing drugs (PIEDs) or life-style drugs as an easy way to control weight. Preliminary data from online sources (e.g. websites, drug forums, e-newsletters) suggest an increased use of cannabis amongst the general population as a PIED due to its putative weight-loss properties. The use of cannabis and/or cannabis-related products to lose weight may represent a new substance-use trend that should be carefully monitored and adequately investigated, especially in light of the well-known adverse psychiatric and somatic effects of cannabis, its possible interaction with other medications/drugs and the unknown and potentially dangerous composition of synthetic cannabimimetics preparations.

Elderly woman with triple-negative metastatic breast cancer successfully treated with metronomic capecitabine.

Triple-negative breast cancer phenotype (estrogen receptor-, progesterone receptor- and human epidermal growth receptor 2-negative) is one of the most aggressive molecular subtypes, accounting for 15-20% of all breast tumors. There is no standard treatment for this setting of patients except anthracyclines and taxanes, but not all elderly patients can tolerate these kinds of agents. We describe the case of an elderly woman affected by triple-negative breast cancer with bone and brain metastases who has been treated for five years with metronomic capecitabine. At the moment, the patient has stable disease and enjoys good quality of life. She had initially been diagnosed with a poor Karnofsky index, which has actually improved from 50 to 90. Metronomic capecitabine treatment has clearly improved her quality of life, as documented by the results of the Functional Assessment of Cancer Therapy Breast.

Adhesion to type V collagen enhances staurosporine-induced apoptosis of adrenocortical cancer cells.

Adrenocortical carcinoma (ACC) is a rare and aggressive tumor characterized by poor prognosis and resistance to conventional chemotherapy. Many chemotherapy agents act determining apoptosis, therefore, studying the responsiveness of ACC to apoptosis inducing molecules, can help to identify possible conditions to promote cancer cell death. Tumor progression is strictly related to the interaction between cancer cells and stroma; yet, extracellular matrix remodeling regulates tumor cell proliferation and apoptosis. At this purpose, we have studied staurosporine-induced apoptosis of ACC cell line H295R adherent to different extracellular matrix molecules. H295R cells grown on plastic showed a low responsiveness to staurosporine, with an apoptotic rate of 24 %, as compared to breast cancer MCF7 cells, with an apoptotic rate of 60 %. The adhesion of H295R cells to type V collagen induced a significant increase of apoptosis up to 52 %; this effect was inhibited by anti-integrin alpha2 antibody. At the same time, the adhesion of H295R cells on polylysine, matrigel, lamimin, fibronectin, and type I-III collagens didn't modify staurosporine-induced apoptosis. Staurosporine-treated H295R cells showed an increase of PARP cleavage and of annexin-V expression, when adherent to type V collagen. Yet, staurosporine induced Akt and Erk activation on H295R cells: the adhesion on type V collagen didn't modify Akt activation, while determined a dramatic inhibition of Erk activation. The described data demonstrate that the adhesion to type V collagen specifically increases the responsiveness of ACC cells to staurosporine-induced apoptosis and that this is probably obtained through the inhibition of Erk activation.

Smoking behaviour and mental health disorders--mutual influences and implications for therapy.

Tobacco use is strongly associated with a variety of psychiatric disorders. Smokers are more likely than non-smokers to meet current criteria for mental health conditions, such as mood disorders, anxiety disorders and psychosis. Evidence also suggest that smokers with psychiatric disorders may have more difficulty quitting, offering at least a partial explanation for why smoking rates are higher in this population. The mechanisms linking mental health conditions and cigarette smoking are complex and likely differ across each of the various disorders. The most commonly held view is that patients with mental health conditions smoke in an effort to regulate the symptoms associated with their disorder. However some recent evidence suggests that quitting smoking may actually improve mental health symptoms. This is particularly true if the tobacco cessation intervention is integrated into the context of ongoing mental health treatment. In this paper we reviewed and summarized the most relevant knowledge about the relationship between tobacco use and dependence and psychiatric disorders. We also reviewed the most effective smoking cessation strategies available for patients with psychiatric comorbidity and the impact of smoking behavior on psychiatric medication.

Pomegranate Juice Metabolites, Ellagic Acid and Urolithin A, Synergistically Inhibit Androgen-Independent Prostate Cancer Cell Growth via Distinct Effects on Cell Cycle Control and Apoptosis.

Ellagitannins (ETs) from pomegranate juice (PJ) are bioactive polyphenols with chemopreventive potential against prostate cancer (PCa). ETs are not absorbed intact but are partially hydrolyzed in the gut to ellagic acid (EA). Colonic microflora can convert EA to urolithin A (UA), and EA and UA enter the circulation after PJ consumption. Here, we studied the effects of EA and UA on cell proliferation, cell cycle, and apoptosis in DU-145 and PC-3 androgen-independent PCa cells and whether combinations of EA and UA affected cell proliferation. EA demonstrated greater dose-dependent antiproliferative effects in both cell lines compared to UA. EA induced cell cycle arrest in S phase associated with decreased cyclin B1 and cyclin D1 levels. UA induced a G2/M arrest and increased cyclin B1 and cdc2 phosphorylation at tyrosine-15, suggesting inactivation of the cyclin B1/cdc2 kinase complex. EA induced apoptosis in both cell lines, while UA had a less pronounced proapoptotic effect only in DU-145. Cotreatment with low concentrations of EA and UA dramatically decreased cell proliferation, exhibiting synergism in PC-3 cells evaluated by isobolographic analysis and combination index. These data provide information on pomegranate metabolites for the prevention of PCa recurrence, supporting the role of gut flora-derived metabolites for cancer prevention.

Phenolic acid concentrations in plasma and urine from men consuming green or black tea and potential chemopreventive properties for colon cancer.

SCOPE: Tea polyphenols are metabolized by the colonic microflora yielding phenolic metabolites, which may contribute to the health benefits of tea. We determined the serum and urine concentrations of phenolic acids, hippuric acid, and polyhydroxyphenyl-γ-valerolactones during green tea (GT) and black tea (BT) administration. The effects of (-)-epigallocatechin gallate (EGCG) and 3,4-dihydroxyphenylacetic acid (3,4-DHPAA) alone and in combination on bioavailability, intracellular metabolism, and antiproliferative activity were determined in HCT-116 colon cancer cells. METHODS AND RESULTS: The concentration of phenolic metabolites was quantified by HPLC with electrochemical detection and MS. Urine concentrations of 4-hydroxyphenylacetic acid (4-HPAA), 3-hydroxyphenylacetic acid (3-HPAA), and polyhydroxy-γ-valerolactones were increased significantly in men drinking GT compared to control. Urine concentration of 3-O-methylgallic acid (3OMGA) was significantly increased in men drinking BT compared to control. Serum 3,4-DHPAA was significantly increased after consumption of GT and BT and 4-HPAA after GT consumption. In vitro treatment of HCT-116 colon cancer cells with 3,4-DHPAA and EGCG exhibited an additive antiproliferative effect, while methylation of 3,4-DHPAA was significantly decreased. 3OMGA exhibited the strongest antiproliferative activity among the phenolic acids. CONCLUSION: The consumption of both, GT and BT, was associated with a significant increase in urinary and serum phenolic acids.

Oxidized low-density lipoproteins impair endothelial function by inhibiting non-genomic action of thyroid hormone-mediated nitric oxide production in human endothelial cells.

BACKGROUND: Thyroid hormone (TH) plays an important role in the modulation of cardiac function, including contractility and systemic vascular resistance (SVR). 3,5,3'-triiodothyronine (T(3)), the active form of TH, induces the activation of endothelial nitric oxide synthase via PI3K/AKT non-genomic signaling. Hypothyroidism is associated with an increase in SVR and serum low-density lipoproteins (LDL) levels, and accumulation of oxidized LDL (oxLDL) may impair endothelial-dependent vascular relaxation. The aim of this study was to investigate the effects of both native LDL (nLDL) and oxLDL on T(3)-mediated AKT phosphorylation, nitric oxide (NO), and cyclic guanosine monophosphate (cGMP) production in human endothelial cells. METHODS: Human umbilical vein endothelial cells were exposed to either nLDL or oxLDL for 3 hours and then stimulated with T(3) (10(-7) M) or pretreated with an antioxidant mixture of vitamins E and C for 12 hours before treatment with LDL. An analysis of AKT phosphorylation was performed by Western blot, and NO production was evaluated by using 4,5-diaminofluorescein diacetate. Intracellular production of cGMP was measured by enzymatic immunoassay. LDL oxidation was carried out by incubating LDL with CuSO(4), and α-tocopherol content of LDL was evaluated by high-performance liquid chromatography. RESULTS: OxLDL impaired T(3)-mediated AKT phosphorylation at serine 473 and significantly decreased the production of both NO (oxLDL+T(3) vs. T(3), 9.79±0.5 AU vs. 80.75±2.8 AU, mean±standard deviation, p<0.0001) and cGMP. Furthermore, pretreatment with the antioxidant mixture obviated the inhibitory effect of LDL on T(3) action. CONCLUSIONS: The results of this study demonstrate that oxLDL may contribute to a blunting of the non-genomic action of T(3) and impair the effect of T(3) on NO and cGMP production in endothelial cells. These data suggest that oxLDL, apart from inducing the atherosclerotic process, may also promote a mechanism of peripheral resistance to T(3,) further amplifying the impact of hypothyroidism on endothelial function by increasing SVR.

Central serous chorioretinopathy as a presenting symptom of endogenous Cushing syndrome: a case report.

PURPOSE: To report a case of Cushing syndrome due to adrenocortical adenoma revealed by central serous chorioretinopathy. MATERIALS AND METHODS: A 45-year-old man presented with blurred vision and metamorphopsia in the left eye. He reported few episodes of high blood pressure in the last 3 months. RESULTS: Visual acuity was 20/40 in the left eye. Fundus oculi examination revealed central serous chorioretinopathy in the left eye. Grade 1 hypertension was found. Increased serum and urinary levels of cortisol and reduced serum levels of ACTH were observed. Diagnosis of Cushing syndrome was made. Computed tomography scan revealed a right adrenal mass that was surgically removed; histologic examination showed an adrenocortical adenoma. Three months after surgical treatment, visual acuity improved to 20/20 and central serous chorioretinopathy completely resolved. CONCLUSIONS: Central serous chorioretinopathy may be the presenting symptom of Cushing syndrome in a patient with adrenocortical adenoma.