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A series of 16 cases of carotid-ophthalmic aneurysm treated by direct approach is reported and the following points are emphasized: [ABSTRACT FROM AUTHOR]

Background: The global economic burden of Diabetes mellitus (DM) is expected to reach US$ 745 billion in 2030. The growing prevalence of the disease, mainly type 2 diabetes, is the result of population aging, nutritional transition, which include growing rates of obesity and consumption of foods high in sugar and fat. Brazil is the fourth country in the number of patients with diabetes globally and follows the global trends, with a continuous increase in prevalence., Objectives: To estimate the economic burden of DM in Brazil, including all direct and indirect costs., Methods: We used a cost-of-illness approach to calculate the total economic burden of DM. We used official healthcare-related statistics referring to 2016., Findings: We estimated the Brazilian economic burden to reach US$ 2.15 billion in 2016, of which 70.6% are indirect costs related to premature deaths, absenteeism, and early retirement. We estimate that if the rate of growth of diabetes prevalence remains in Brazil, direct and indirect costs of diabetes will more than double by 2030 (an increase of 133.4% or 6.2% per year)., Conclusion: Our results are in accordance with the literature that shows that indirect costs are more relevant in low- and middle-income countries due to poorer access to health care, which result in higher mortality rates from non-communicable diseases. However, due to the potentially underestimated prevalence of diabetes in Brazil and the lack of access to nationwide private healthcare costs, we estimate costs of diabetes in Brazil to be higher than the conservative results we found. The onset of the COVID-19 pandemic is likely to result in even greater costs than what we estimated., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2022 The Author(s).)

A series of isoniazid derivatives bearing a phenolic or heteroaromatic coupled frame were obtained by mechanochemical means. Their pH stability and their structural (conformer/isomer) analysis were checked. The activity of prepared derivatives against Mycobacterium tuberculosis cell growth was evaluated. Some compounds such as phenolic hydrazine 1a and almost all heteroaromatic ones, especially 2 , 5 and 7 , are more active than isoniazid, and their activity against some M. tuberculosis MDR clinical isolates was determined. Compounds 1a and 7 present a selectivity index >1400 evaluated on MRC5 human fibroblast cells. The mechanism of action of selected hydrazones was demonstrated to block mycolic acid synthesis due to InhA inhibition inside the mycobacterial cell.

Forest management could potentially affect organisms in all forest habitats. However, aquatic communities in water-filled tree-holes may be especially sensitive because of small population sizes, the risk of drought and potential dispersal limitation. We set up artificial tree holes in forest stands subject to different management intensities in two regions in Germany and assessed the influence of local environmental properties (tree-hole opening type, tree diameter, water volume and water temperature) as well as regional drivers (forest management intensity, tree-hole density) on tree-hole insect communities (not considering other organisms such as nematodes or rotifers), detritus content, oxygen and nutrient concentrations. In addition, we compared data from artificial tree holes with data from natural tree holes in the same area to evaluate the methodological approach of using tree-hole analogues. We found that forest management had strong effects on communities in artificial tree holes in both regions and across the season. Abundance and species richness declined, community composition shifted and detritus content declined with increasing forest management intensity. Environmental variables, such as tree-hole density and tree diameter partly explained these changes. However, dispersal limitation, indicated by effects of tree-hole density, generally showed rather weak impacts on communities. Artificial tree holes had higher water temperatures (on average 2°C higher) and oxygen concentrations (on average 25% higher) than natural tree holes. The abundance of organisms was higher but species richness was lower in artificial tree holes. Community composition differed between artificial and natural tree holes. Negative management effects were detectable in both tree-hole systems, despite their abiotic and biotic differences. Our results indicate that forest management has substantial and pervasive effects on tree-hole communities and may alter their structure and functioning. We furthermore conclude that artificial tree-hole analogues represent a useful experimental alternative to test effects of changes in forest management on natural communities.

In the present paper, we report the synthesis via catalytic Michael reaction and biological results of a series of 3-heteryl substituted pyrrolidine-2,5-dione derivatives as moderate inhibitors against Mycobacterium tuberculosis H37Rv growth. Some of them present also inhibition activities against InhA., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

The synthesis of C-7/C-7-linked ciprofloxacin (CP) and C-6/C-6-linked levofloxacin (LV) derivatives with modulated lipophilicity is described herein. The synthesized compounds, along with the monomeric analogs described previously, were evaluated in vitro for (i) their growth inhibitory effect against five human cancer cell lines, (ii) their antibacterial activity against Gram-positive Staphylococcus aureus and Enterococcus hirae and Gram-negative Escherichia coli and Pseudomonas aeruginosa strains and (iii) their antimycobacterial activity. The most efficient derivatives as antiproliferative agents (C-7/C-7-linked CP 7e and C-6/C-6-linked LV 11f) displayed IC(50) values in the 0.1-8.7 and 0.2-0.7 μM ranges respectively while IC(50) values for parent CP and LV ranged from 89 to 476 μM and from 67 to 622 μM respectively depending on the cell line. A specific antibacterial activity against S. aureus was found for the monomeric and dimeric derivatives of CP. The most efficient derivative against S. aureus (monomeric oxoethyloctanoate CP derivative 3d) displayed MIC <1 nM. Monomeric alkanoyloxymethyl LV esters (9a,c,e,f) and C-6/C-6-linked LV derivatives (11f-h) were the most efficient derivatives as antimycobacterial agents with MIC and IC(50) values in the 2.5-5 μM and 1.3-≤ 2.5 μM ranges respectively while MIC and IC(50) values for parent LV were 2.5 and 0.8 μM, respectively., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

A convenient route for the synthesis of some acyloxymethyl esters and carboxamides of levofloxacin (LV) with modulated lipophilicity is described. The synthesized compounds were evaluated in vitro for their growth inhibitory effect in five human cancer cell lines. The most efficient LV derivatives (ester 2e and amide 4d) displayed IC(50) values in the 0.2-2.2 μM range, while IC(50) values for parent LV ranged between 70 and 622 μM depending on the cell line. The esters displayed no in vivo toxicity up to 80 mg/kg when administered intraperitoneally. This study thus shows that LV analogs displayed antitumor efficacy, at least in vitro, a feature that appeared to be independent from the lipophilicity of the grafted substituent., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Ciprofloxacin (CP), an antibiotic has been shown to have antiproliferative and apoptotic activities in several cancer cell lines. Moreover, several reports have highlighted the interest of increasing the lipophilicity to improve the antitumor efficacy. These studies have led us to synthesize new CP derivatives of various lipophilicities and to evaluate their activity in five human cancer cell lines. With an easy and cost-efficient procedure, 31 7-((4-substituted)piperazin-1-yl) derivatives of CP were prepared that displayed IC(50) values ranging from microM to mM concentrations and are non-toxic in vivo in healthy mice as shown by their maximal tolerated dose (MTD) indices >80 mg/kg. Several derivatives displayed higher in vitro antitumor activity than parent CP however this was not dependent on the lipophilicity of the substituent. Among all synthesized derivatives, the most potent were 2 and 6h whose IC(50) values were 10 microM in three (derivative 2) or four (derivative 6h) cancer cell lines.

Proliferative vitreoretinopathy (PVR), the most serious complication causing retinal detachment surgery to fail, is one of the leading causes of vision-loss in developed countries. The pharmaceutical treatment of this disease, located in the posterior segment of the eye, is problematic because it is difficult to achieve effective drug levels in the vitreous and the retina through conventional forms of administration (topical or systemic). Intravitreal injections can deliver drugs to the retina without the side-effects associated with systemic administration. However, because PVR is a long-term complication and the half-life of most drugs in the vitreous cavity is short, repeated injections are needed but this can cause complications. Recent advances in ocular drug delivery methods and the development of novel bioactive compounds could lead to new ways for the treatment of PVR. This review will summarize recent literature concerning intraocular drug delivery of biopharmaceutical agents for the treatment and prevention of PVR.

Various alkylcarbonyloxymethyl esters of nalidixic acid ranging from 3 to 15 carbon units in the pro-moiety have been prepared and assessed as potential prodrugs. Their chromatographic retention factors k', silicone oil solubilities and in vitro conversion to nalidixic acid by a commercial esterase were determined together with their in vitro antimicrobial activity and cytotoxicity. The preliminary results suggest that silicone oil may have potential for the intra-ocular delivery of antibacterial compounds. Moreover, the in vitro release rate can be controlled by the lipophilicity of the prodrug.

A series of 15 arteriovenous malformations (AVMs) of the corpus callosum--9% of 170 intracranial AVMs admitted to the School of Medicine of the University of Rome during a 30-yr period--was studied. In all cases the lesion concerned mainly the corpus callosum, although in some it also involved the surrounding structures, such as septum pellucidum, tela choroidea, and the mesial hemisphere. These malformations are divided into three groups, namely, those involving mainly the genu, the truncus, or the splenium of the corpus callosum. The last predominated in the present series. Each type has a peculiar angiographic appearance. In general these lesions are fed by branches from the anterior cerebral and/or posterior cerebral arteries, although in some cases minor contributions from the middle cerebral artery may also be present. Vascularization is often bilateral. Venous drainage occurs through the inferior and/or superior sagittal sinuses and/or the Galen system. As to clinical presentation, Subarachnoid Hemorrhage (SAH) is the usual presenting symptom and tends to recur frequently. Neurological localizing symptoms are infrequent, as are seizures; psychological symptoms are an exception. Of the 4 cases managed conservatively, only one had no further episodes of bleeding and remained free of complaints. On the other hand, surgical results of the 11 operated patients were satisfactory, in the sense that no mortality and low morbidity were recorded. Accordingly, surgical treatment of AVMs of the corpus callosum is recommended as a rule.

The International Cooperative Study on the Timing of Aneurysm Surgery included 68 participating centers from 16 different countries. Eight Italian neurosurgical units participated in the Study: Bellaria Hospital, Bologna; Neurological Institute of Milan, Milan; University Hospital, Brescia; University of Milan, Milan; University of Padova, Padova; University of Rome, Rome; Civil Hospital, Verona; and Civil Hospital, Vicenza. The overall case contribution from the Italian centers was 485 cases, 14.1% of the total study population. As compared to the other centers included in the Study, the Italian centers exhibited a higher percentage of patients with impaired consciousness; a later interval of planned surgery from SAH; frequent use of preoperative lumbar drainage, as well as antihypertensives, anticonvulsants, antifibrinolytics, steroids, diuretics and LMW dextran; and less frequent use of sedatives and narcotics. The individual Italian centers differed significantly in regard to patient characteristics and preoperative therapeutic modalities. There was a relatively high number of stuporous or comatose patients admitted to Centers 1, 7 and 8, very few admitted to Centers 5 and 6, and none admitted to Center 2. The different distribution of key prognostic factors prevents a direct comparison of the overall management results of the centers. A stratification of the patients according to a risk scale and/or a prognostic model is required for comparison of the management results.

The prognostic significance of admission leukocytosis with respect to ischemic complications of subarachnoid hemorrhage was retrospectively investigated in a series of patients with recently ruptured intracranial aneurysms. The present study concerned 47 consecutive cases admitted within 72 hours following the last hemorrhage, in the years 1982-1984. There was no difference in the admission WBC counts between patients who subsequently deteriorated due to ischemic complications and those who did not. However, the cell count rose significantly at the time of the clinical manifestations of ischemia, possibly as a result of structural damage of brain tissue and/or increased sympathetic and adrenocortical activity. The possible contribution of leukocytes to the pathogenesis of ischemic damage following subarachnoid hemorrhage--perhaps through the release of leukotrienes--will require further investigation.

This paper analyzes the clinical, diagnostic and surgical data of 18 benign extramedullary tumors at the foramen magnum extending into the posterior fossa and the spinal canal. These cases represent 30% of 60 foramen magnum tumors operated on between 1952 and 1978, among 4187 brain tumors and 587 tumors of the spinal cord. Foramen magnum meningiomas constitute 11 of this series (1.2% of 873 meningiomas, 113 of which were spinal). The considerable difficulty in early diagnosis is emphasized. However, in the present series, myelography showed positive findings in all cases, and angiography in most of them. CT scan, performed in one case, demonstrated the lesion. Surgical mortality was 11% (two deaths). On both patients who died after the operation, multiple surgical procedures had been performed because of erroneous diagnoses made in another unit. At the time of operation neurological symptoms were very advanced, and large tumors were located anteriorly. The review of the remaining patients showed a regression of preoperative symptoms with good to excellent results in all. No recurrences were recorded.

This study concerns 51 cases of cystic pilocytic astrocytoma of the cerebral hemispheres. At operation these tumors closely resembled cerebellar astrocytomas, presenting as a big cyst contiguous with the lateral ventricle and containing a small mural nodule. The nodule was in a deep location in 26 cases, and always showed marked contrast enhancement on computerized tomography scans. The most frequent presenting symptom was epilepsy (68%), and the most common sign was papilledema (85%). The major goal of surgery was extirpation of the nodule. The follow-up period of the 34 cases available for long-term review ranged from 6 to 31 years (mean 17 years). Of these, 28 patients (82%) had a good outcome; four (12%) had a fair result, and two (6%) had a poor response. An analysis of these results shows that total extirpation of the mural tumor was associated with the best outcome, whether or not the cyst wall was completely removed. Radiation therapy was irrelevant to the prognosis for these patients. On the other hand, partial excision of the nodule, correlated with the deep location of the tumor, was the cause of the two poor results in this series and resulted in multiple operations for recurrences in two other patients. Nevertheless, two of these patients are still alive and well many years after incomplete surgical treatment. On the basis of this study, the importance of recognizing the occurrence of this "benign" tumor of the cerebral hemispheres is stressed, and the hypothesis of a common origin from subependymal glia of all pilocytic astrocytomas is supported.

The authors report their experience and long-term results in the surgical treatment of 61 tentorial meningiomas. These cases were operated on between 1951 and 1985 and represented 4.8% of all intracranial meningiomas operated on in that period. The mean duration of clinical history was 29 months, except for cases of meningioma of the posteromedial border, for which it was 5 years. Plain x-ray films and cerebral angiograms were obtained in all cases. Computerized tomography, performed in the last 20 cases (32.7%), supplied much better lesion topography and early diagnosis. The tumor site was posterolateral in 26 cases (42.6%), anterolateral in 14 (22.9%), posteromedial in eight (13.1%), at the free border in seven (11.4%), and in the tentorium itself in six (9.8%). Lateral and medial tumors with solely or mainly supratentorial development were approached from above. The approach from below was reserved for meningiomas with subtentorial involvement only. In meningiomas with both supra- and subtentorial growth, a supratentorial bone flap was combined with a suboccipital craniectomy using a retromastoid incision. The mortality rate was 9.8%. Of the remaining 42 patients, who were followed for at least 5 years, long-term results were good in 26 cases (61.9%), fair in 11 (26.2%), and poor in five (11.9%). Postoperative complications arose in 34% of the patients, but cleared in 27%.

The authors present a consecutive series of 145 patients admitted to the Institute of Neurosurgery of Rome University with an intracranial arteriovenous malformation (AVM). Of these, 95 received surgical care, and 50 were treated conservatively. Total removal of the AVM was performed in all but three of the patients treated surgically, and all underwent postoperative angiography. The postoperative mortality was 6.3%. A long-term follow-up study showed a mortality rate of 20% in the group of patients receiving conservative treatment, while no recurrence of bleeding was observed in the surgical group. The choice of treatment of these malformations is still an open question. The authors' contribution to the discussion is based on the late results of both surgical and conservative treatment.