COVID-19 emergency: from a general hospital to a covid hospital in one week, an Italian experience.

Abstract: Aim of this letter is to describe the reconversion process of our general hospital, in just one week, into a COVID-19 Hospital. The working strategy allowed to quickly find the spaces, identify the working group, reshape the hospital organizational structure, redesign the flows and patient/health workers pathways. The hospital provided for a progressive activation of COVID-19 beds following the philosophy of the intensity of care. The main results were on management, flows, PPE and hygiene areas. Although some problems came out in the beginning, this fast hospital reconversion model may be replicated in the future to face similar epidemic or pandemic outbreaks.

Diphtheria toxin IgG levels in military and civilian blood donors in Rio de Janeiro, Brazil

Serologic data on diseases that are preventable by vaccines are necessary to evaluate the success of immunization programs and to identify susceptible subgroups. In the present study, we determined serum IgG levels against diphtheria toxin of military and civilian blood donors (N = 75; 69.3 percent males and 30.7 percent females) aged 18-64 years, from the Brazilian Army Biology Institute, Rio de Janeiro, using a commercial diphtheria kit (Diphtheria IgG ELISA; IBL, Germany). Most (63 percent) unprotected military donors were from the older age group of 41 to 64 years. In contrast, the majority (71 percent) of young military donors (18 to 30 years) were fully protected. About half of the military donors aged 31 to 40 years were protected against diphtheria. Among the civilians, about 50 percent of persons aged 18 to 30 years and 31 to 40 years had protective antibody levels against diphtheria as also did 64 percent of individuals aged 41 to 64 years. All civilians had a similar antibody response (geometric mean = 0.55 IU/mL) independent of age group. Military donors aged 18-30 years had higher IgG levels (geometric mean = 0.82 IU/mL) than military donors of 41-64 years (geometric mean = 0.51 IU/mL; P > 0.05). In conclusion, the existence of a considerable proportion of susceptible adults supports the position that reliable data on the immune status of the population should be maintained routinely and emphasizes the importance of adequate immunization during adulthood.

Diphtheria toxin IgG levels in military and civilian blood donors in Rio de Janeiro, Brazil.

Serologic data on diseases that are preventable by vaccines are necessary to evaluate the success of immunization programs and to identify susceptible subgroups. In the present study, we determined serum IgG levels against diphtheria toxin of military and civilian blood donors (N = 75; 69.3% males and 30.7% females) aged 18-64 years, from the Brazilian Army Biology Institute, Rio de Janeiro, using a commercial diphtheria kit (Diphtheria IgG ELISA; IBL, Germany). Most (63%) unprotected military donors were from the older age group of 41 to 64 years. In contrast, the majority (71%) of young military donors (18 to 30 years) were fully protected. About half of the military donors aged 31 to 40 years were protected against diphtheria. Among the civilians, about 50% of persons aged 18 to 30 years and 31 to 40 years had protective antibody levels against diphtheria as also did 64% of individuals aged 41 to 64 years. All civilians had a similar antibody response (geometric mean = 0.55 IU/mL) independent of age group. Military donors aged 18-30 years had higher IgG levels (geometric mean = 0.82 IU/mL) than military donors of 41-64 years (geometric mean = 0.51 IU/mL; P > 0.05). In conclusion, the existence of a considerable proportion of susceptible adults supports the position that reliable data on the immune status of the population should be maintained routinely and emphasizes the importance of adequate immunization during adulthood.

Impact of highly active antiretroviral therapy on organ-specific manifestations of HIV-1 infection.

In the last 10 years, interesting results have been reported concerning the impact of highly active antiretroviral therapy (HAART) on the changing pattern of organ-specific manifestations of HIV-1 infection. There has been a clear step-wise reduction in the incidence of several opportunistic infections (OIs), particularly Pneumocystis carinii pneumonia, whereas a nonsignificant reduction in incidence has been observed for other organ-specific diseases, including invasive cervical cancer and Hodgkin disease. In addition, several organ-specific manifestations, including HIV-associated nephropathy, wasting syndrome and cardiomyopathy, are a direct consequence of damage by HIV-1, and so HAART may have a therapeutic effect in improving or preventing these manifestations. Finally, the introduction of HAART has seen the emergence of several complications, termed immune reconstitution inflammatory syndrome, which includes OIs such as cytomegalovirus vitritis, Mycobacterium avium complex lymphadenitis, paradoxical responses to treatment for tuberculosis, and exacerbation of cryptococcosis. Because not all HIV-1 organ-specific manifestations are decreasing in the HAART era, this review will analyse the influence of HAART on several organ-specific manifestations, and in particular OIs related to several organs, cerebral disorders and HIV-1-related neoplasia.

Cyclic adenosine monophosphate-dependent phosphorylation of mammalian mitochondrial proteins: enzyme and substrate characterization and functional role.

A study is presented on cyclic adenosine monophosphate- (cAMP-) dependent phosphorylation of mammalian mitochondrial proteins. Immunodetection with specific antibodies reveals the presence of the catalytic and the regulatory subunits of cAMP-dependent protein kinase (PKA) in the inner membrane and matrix of bovine heart mitochondria. The mitochondrial cAMP-dependent protein kinase phosphorylates mitochondrial proteins of 29, 18, and 6.5 kDa. With added histone as substrate, PKA exhibits affinities for ATP and cAMP and pH optimum comparable to those of the cytosolic PKA. Among the mitochondrial proteins phosphorylated by PKA, one is the nuclear-encoded (NDUFS4 gene) 18 kDa subunit of complex I, which has phosphorylation consensus sites in the C terminus and in the presequence. cAMP promotes phosphorylation of the 18 kDa subunit of complex I in myoblasts in culture and in their isolated mitoplast fraction. In both cases cAMP-dependent phosphorylation of the 18 kDa subunit of complex I is accompanied by enhancement of the activity of the complex. These results, and the finding of mutations in the NDUFS4 gene in patients with complex I deficiency, provide evidence showing that cAMP-dependent phosphorylation of the 18 kDa subunit of complex I plays a major role in the control of the mitochondrial respiratory activity.

Nevirapine or efavirenz combined with two nucleoside reverse transcriptase inhibitors compared to HAART: a meta-analysis of randomized clinical trials.

PURPOSE: A meta-analysis of randomized controlled trials (RCTs) was performed to evaluate effectiveness and tolerability of triple antiretroviral therapy regimens in HIV-infected patients. METHOD: RCTs including the nonnucleoside reverse transcriptase inhibitors (NNRTIs) nevirapine (NVP) or efavirenz (EFV) compared to two nucleoside reverse transcriptase inhibitor (NRTI) regimens and to three-drug regimens based on two NRTIs and one protease inhibitor (PI; highly active antiretroviral therapy [HAART]) were analyzed by Peto's method. RESULTS: A significant virological response was observed in patients treated with NNRTIs (odds ratio [OR] 3.6; 95% CI, 2.2-6.0), particularly in naïve patients (OR 7.4; 95% CI, 4.1-13.5). A fair reduction of HIV disease progression was also observed in patients treated with NNRTIs (OR 0.8; 95% CI, 0.6-1.0). Moreover, a significantly lower rate of HIV progression was observed in patients with a CD4 + lymphocyte count below 100/mm(3). Five RCTs comparing two NRTIs and one NNRTI to HAART were subsequently evaluated. A slightly higher rate of virological response was observed with NNRTIs (OR 1.6; 95% CI, 1.1-2.1), whereas no difference was observed concerning progression of HIV disease. CONCLUSION: Antiretroviral therapy including NVP or EFV was more effective in reducing viral load than therapy with only two NRTIs and was slightly more effective than HAART. Effectiveness in delaying HIV disease progression was less evident, even though lower rate of progression was observed in patients with advanced HIV infection compared to two NRTIs alone.

Binocular detection of masked patterns in young and old observers.

A visual pattern embedded in noise is detected appreciably better when the stimulus complex contains interocular cues (dichoptic condition) than when such cues are absent (binoptic condition). In a recent study (F. Speranza, G. Moraglia, & B. A. Schneider, 1995) the authors showed that the relative difference between binoptic and dichoptic thresholds does not change with age. However, older adults showed higher binoptic and dichoptic thresholds, thus suggesting an age-related difficulty with degraded stimulation. In this article the authors first replicated these findings and proceeded next to investigating whether age-related changes in processing efficiency, additive internal noise, and the spatial frequency bandwidth of the detecting filters could account, separately or concurrently, for the elevated thresholds in noise exhibited by the older adults. Results indicate that this increase is not attributable to age-related changes in filter bandwidth or internal noise. Rather, the findings can be explained in terms of a decrease in processing efficiency with age.

Serum levels of interleukin-18 in patients with uncomplicated Plasmodium falciparum malaria.

Interleukin (IL)-18, a newly discovered cytokine produced primarily by macrophages, has been shown to induce gamma interferon (IFN-gamma) production by natural killer cells, to induce the T helper type 1 response. To further elucidate the role of this cytokine in uncomplicated malaria caused by Plasmodium falciparum, serum levels of IL-18, and gamma interferon (IFN-gamma), determined by an immunoenzymatic assay, were analyzed in 40 adult patients, and in 15 healthy control subjects. A significant increase in serum levels of IL-18 was observed in patients with uncomplicated P. falciparum malaria on admission, whereas serum levels of IFN-gamma tended to increase although not significantly. Serum levels of IL-18 decreased three days later, but still remained significantly high, whereas IFN-gamma levels returned to normal levels compared to the controls. No significant correlation was found between parasitemia and serum levels of IL-18 and IFN-gamma. The increase of IL-18 levels during acute and recovery phases of uncomplicated P. falciparum malaria may reflect a proinflammatory role of IL-18 in these patients. An early and effective immune response regulated by proinflammatory Th1 cytokines, including tumor necrosis factor (TNF), interleukin (IL)-12, and possibly IFN-gamma may limit the progression from uncomplicated malaria to severe and life-threatening complications.

Monocular unmasking of noise-embedded patterns.

Binocular disparity cues may help an observer "unmask" a target in a background, thereby enhancing its detectability (e.g., Moraglia & Schneider, 1992). Here, we sought to determine whether similar effects could be produced by monocular displacement cues resulting from a two-frame sequential presentation of a Gabor pattern (a sinusoidal modulation of luminance combined with a Gaussian modulation of local contrast) embedded in an unvarying field of two-dimensional Gaussian noise. The Gabor in the second frame was spatially displaced relative to its location in the first frame; the horizontal displacement corresponded to a phase shift of the peak spatial frequency of the Gabor of 0 degree, 90 degrees, 180 degrees, 360 degrees, or 540 degrees. Monocular detection thresholds for the Gabor were appreciably lower for the 90 degrees, 180 degrees, and 540 degrees shift, than for the 0 degree and 360 degrees values. We explain these findings in terms of a model that constitutes the monocular analog of our summation model of binocular unmasking.

How aging affects the reading of words in noisy backgrounds.

Young and old adults were shown simple sentences masked by visual noise. In half of the sentences, the final word was predictable; in the other half, it was not. The older participants were able to identify the same number of final words as the younger ones only when the intensity of the visual noise was significantly diminished. However, the difference in the number of correct identifications between predictable and unpredictable conditions was higher for the older observers than for the younger observers, indicating that older observers benefit from context more.

Levels of the bcl-2 protein, fibronectin and alpha(5)beta(1) fibronectin receptor in HIV-1-infected patients with Kaposi's sarcoma.

Kaposi's sarcoma (KS) is an angioproliferative disease characterized by proliferation of neoplastic cells (spindle cells) mixed with endothelial and inflammatory cells. In this study we evaluated the role of the adhesive glycoprotein, fibronectin (FN) and its receptor alpha(5)beta(1) (FNR), and the proto-oncogene bcl-2, an anti-apoptotic protein. Significantly decreased serum levels of FN were noted in HIV-1-infected patients with KS, whereas serum levels of FNR were significantly increased in the same patients. Furthermore, increased FNR expression was observed on CD4 cells from KS patients. Serum levels of bcl-2 protein were significantly decreased in asymptomatic seropositive patients, whereas HIV-1-infected patients with KS showed increased serum levels of bcl-2. These results provide further information about interaction between integrins and the extracellular matrix and bcl-2 protein that can support cell survival either of neoplastic cells or endothelial and inflammatory cells.

Levels of nitric oxide, gamma interferon and interleukin-12 in AIDS patients with toxoplasmic encephalitis.

The production of nitric oxide (NO) by macrophages is important for the killing of intracellular pathogens, such as Toxoplasma gondii. Gamma interferon (IFN-gamma) and lipopolysaccharide stimulate NO production. The aim of this study was to investigate the importance of NO, IFN-gamma and interleukin-12 (IL-12) in the host immune response in AIDS patients suffering from toxoplasmic encephalitis (TE). It was demonstrated that the production of NO, detected as nitrite/nitrate in the sera and in the cerebrospinal fluid (CSF) of 32 AIDS patients with TE, was normal. In addition, levels of IFN-gamma in the sera and in the CSF of patients with TE were not increased. In contrast, serum levels of IL-12 in these patients were significantly increased (6.5 +/- 7.1 pg/ml; P = 0.0368), compared to the control patients (1.7 +/- 3.5 pg/ml). Furthermore, increased but not significant levels of IL-12 were also observed in the CSF of patients with TE (2.2 +/- 4.7 pg/ml; controls: 0.5 +/- 1.9 pg/ml). The results of this study indicate that reactivation or recurrence of T. gondii infection in HIV-1-infected patients is probably due to a down-regulation of IFN-gamma along with a resulting non-optimal NO activity.

Binocular vision enhances phase discrimination by filtering the background.

Previous studies have shown that the detectability of a noise-masked target can be enhanced under stereoscopic viewing when the target's interocular disparity differs from that of the noise. This enhanced detectability can be accounted for by a model postulating that the binocular system linearly sums the left-eye and right-eye views of a visual scene. This model also predicts enhanced phase discrimination under specifiable interocular disparities of target and noise. Two experiments were conducted in which subjects were asked to discriminate between two luminance patterns (target and foil) that differed only in phase. The target patterns were constructed by summating two vertical sinusoidal gratings in which the phase difference between the higher and the lower spatial frequency gratings was 45 degrees. The foils contained the same two component frequencies, with a phase difference of -45 degrees. Thus, targets and foils were mirror images of one another. The ability of subjects to discriminate between these stereoscopically viewed mirror-image patterns was investigated under two sets of interocular disparities: those that, according to our model, would unmask one or both spatial frequency components, and those that would leave both components masked by the noise. Phase discrimination was enhanced only when both component frequencies of the target and foil were unmasked. The implications of these findings for template-matching and phase-discrimination models of pattern discrimination are considered.

Regulation of inflammatory responses to Bordetella pertussis by N(G)-monomethyl-L-arginine in mice intranasally infected.

To investigate effect of MMLA, an inhibitor of nitric oxide (NO) production, on regulation of inflammatory responses to Bordetella pertussis infection, mice were infected intranasally, and treated with various concentrations of MMLA. Ten days after infection, mice treated with MMLA at dosage of 100 mg/kg, given intraperitoneally in a single dose or for 5 consecutive days, showed at histopathologic examination, a significant decrease of intensity of inflammation (scores, 0.6 +/- 0.2 and 0.9 +/- 0.5 respectively). A decrease of cellular accumulation of neutrophils and lymphocytes in the bronchoalveolar lavage (BAL) fluid was observed in infected mice treated with MMLA, especially at dosage of 10 mg/kg, given in a single dose intraperitoneally. In addition, BP-infected mice treated with MMLA (100 mg/kg, intraperitoneally) for 5 consecutive days showed higher mortality rate than untreated mice infected with B. pertussis, and the number of B. pertussis in lungs of mice treated with MMLA was significantly increased. However, MMLA treatment of infected mice had some effect on levels of IFN-gamma and nitrite/nitrate (end-stable products of NO) in the BAL fluid. This study indicates that NO may play a role either as microbiocidal agent or as a modulator of immune regulation, inasmuch as it may upregulate tissue inflammatory response to B. pertussis.

Meningoencephalitis caused by human herpesvirus-6 in an immunocompetent adult patient: case report and review of the literature.

Human herpesvirus-6 (HHV-6) is the etiologic agent of roseola infantum, and has been implicated as a possible cause of encephalitis in pediatric and adult patients. A case of meningoencephalitis in an otherwise healthy, immunocompetent 59-year-old woman is described. The diagnosis of HHV-6 meningoencephalitis was confirmed by detecting viral DNA in cerebrospinal fluid collected in the acute stage of the disease by polymerase chain reaction. The patient was treated with acyclovir and recovered without any sequelae. The current knowledge of the pathophysiology, clinical course and outcome of HHV-6 meningoencephalitis in immunocompetent adult patients is also reviewed.

A retrospective study of treatment of cerebral toxoplasmosis in AIDS patients with trimethoprim-sulphamethoxazole.

AIMS OF THE STUDY: a retrospective study was designed to evaluate efficacy and tolerance of trimethoprim-sulphamethoxazole (TMP-SMZ) in AIDS patients with cerebral toxoplasmosis (TE). PATIENTS AND METHODS: we reviewed 471 patients with AIDS, and we analysed 71 AIDS patients with TE, who received intravenous therapy with TMP-SMZ (TMP: 10 mg/kg/day, SMZ: 50 mg/kg/day) for 4 weeks. RESULTS: 35 patients (49.2%) had a complete regression of clinical signs, and a complete resolution of radiological lesions was noted in 41 patients (57.7%). Improvement of clinical signs and radiological lesions were observed in 27 patients (38%), and in nine patients (12.6%), respectively. In contrast, nine patients (12.6%) did not show any clinical change, or worsened. Twenty-two patients (30.9%) suffered from adverse cutaneous reactions, whereas many patients had haematological toxicity. CONCLUSIONS: TMP-SMZ seems to be an efficient therapy for TE in AIDS patients, although further prospective, randomized therapeutic trials are required to confirm these results.

A retrospective study on the efficacy and safety of amphotericin B in a lipid emulsion for the treatment of cryptococcal meningitis in AIDS patients.

To evaluate the efficacy and safety of Amphotericin B dissolved in dextrose (Amb) or in a lipid emulsion (Intralipid, Amb-IL) in AIDS patients with cryptococcal meningitis, we conducted a retrospective study in 30 AIDS patients with cryptococcal meningitis. A clinical complete resolution was obtained in 11 patients (55%) treated with Amb, and in six patients (60%) treated with Amb-IL. Intralipid did not decrease the infusion-related adverse effects, in particular nephrotoxicity and anaemia. Our results indicate that Amb-IL formulation is useful in the treatment of cryptococcal meningitis in AIDS patients, but it does not reduce the infusion-related adverse events.

Levels of circulating nitrate/nitrite and gamma interferon not increased in uncomplicated malaria.

The purpose of this study was to evaluate nitric oxide (NO) activity in patients with uncomplicated malaria. Lipopolysaccharide and gamma interferon (IFN-gamma) are potent inducers of NO by inducing production of NO synthase. NO activity was determined by measuring serum levels of nitrite/nitrate (metabolic end products of NO), and IFN-gamma in patients with uncomplicated malaria, mostly caused by Plasmodium falciparum. Neither serum levels of nitrite/nitrate nor of IFN-gamma were significantly increased in patients with uncomplicated malaria, especially in patients with P. falciparum infection, and in those with high parasitaemia. These results show that NO cannot play a role in uncomplicated malaria, and it is still debatable if NO production in this infection has beneficial or detrimental effects.

Randomized trial of trimethoprim-sulfamethoxazole versus pyrimethamine-sulfadiazine for therapy of toxoplasmic encephalitis in patients with AIDS. Italian Collaborative Study Group.

The aim of the present pilot study was to compare the efficacy and safety of trimethoprim (TMP) and sulfamethoxazole (SMX) with those of the standard therapy pyrimethamine (P)-sulfadiazine (S) for the treatment of toxoplasmic encephalitis in patients with AIDS. This was a pilot, multicenter, randomized, and prospective study. Patients were randomly assigned to receive TMP (10 mg/kg of body weight/day) and SMX (50 mg/kg/day) or P (50 mg daily) and S (60 mg/kg/day) as acute therapy (for 4 weeks) and then as maintenance therapy for 3 months at half of the original dosage. Seventy-seven patients were enrolled and randomized to the study: 40 patients were treated with TMP-SMX and 37 were treated with P-S. There was no statistically significant difference in clinical efficacy during acute therapy. In contrast, patients randomized to TMP-SMX appeared more likely to achieve a complete radiologic response after acute therapy. Adverse reactions were significantly more frequent in patients treated with P-S, and skin rash was the most common adverse event noted in these patients. In conclusion, the results of the study suggest that TMP-SMX appears to be a valuable alternative to P-S, in particular in patients with opportunistic bacterial infections.