PubMed Health⌕ Search

Biomedical subjects

C Messa

Publications and source records attributed to C Messa.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effect of Helicobacter pylori infection on gastric emptying and gastrointestinal hormones in dyspeptic and healthy subjects.

There is no general agreement as regards the effect of Helicobacter pylori infection on gastric emptying in patients with functional dyspepsia. Food releases several gastrointestinal hormones, and some of these are known to contribute to the regulation of gastric emptying. The aim of this study was to investigate the influence of H. pylori on gastric emptying in dyspeptic and healthy subjects and to verify whether different hormone secretion patterns are affected by the presence of the bacterium. Twenty-seven patients affected by functional dyspepsia and 30 asymptomatic healthy subjects entered the study. H. pylori presence was assessed in controls by IgG antibodies to H. pylori and [13C] urea breath test, and that in patients by Warthin-Starry stain on gastric biopsies. After ingesting a standard solid-liquid meal, an ultrasound examination of gastric emptying was performed. Plasma concentrations of gastrin, cholecystokinin, and pancreatic polypeptide were measured in the fasting and postprandial period for 4 hours. The incidence of H. pylori infection was not higher in functional dyspepsia patients than in controls. As regards gastric emptying, no difference was detected between patients and controls with and without H. pylori infection. On the contrary, the presence of H. pylori infection determined alterations in gastrin levels, which were higher in controls than in patients. Basal CCK levels were higher in the H. pylori-negative patients than H. pylori-positive patients and controls. In conclusion, H. pylori infection seems not to cause alterations in gastric emptying, but rather alterations in gastrin levels. In contrast, the altered levels of CCK account for its involvement in the pathophysiology of H. pylori-negative dyspepsia.

Adolescent↗
PubMed2001

Circulating cytokines and gastrin levels in asymptomatic subjects infected by Helicobacter pylori (H. pylori).

The pathophysiology of hypergastrinemia in H. pylori infection has been largely investigated and different reports clearly show that the infected antrum has a marked inflammatory response with a suggestive local production of cytokines. Notwithstanding, a few data are available on the circulating levels of cytokines and gastrin in the asymptomatic people carrying H. pylori infection. Thus, aim of the study was to evaluate circulating proinflammatory cytokines [Interleukin (IL)-8, Interleukin (IL)-10, Interferon (IFN)-gamma, and Tumor Necrosis Factor (TNF)-alpha] and gastrin levels in H. pylori positive asymptomatic subjects vs. H. pylori negative ones. To this end, thirty healthy volunteers with no digestive symptoms or systemic disease were enrolled and H. pylori infection was identified by a 13C-urea breath test. Plasma levels of gastrin were determined using the RIA kit whereas IL-8, TNF-alpha, IL-10, and IFN-gamma levels in serum were measured with a solid-phase ELISA. Fifteen infected people showed significantly higher gastrin and TNF-alpha levels than uninfected subjects. On the contrary, IL-8 levels were significantly higher in the uninfected subjects than in H. pylori positive ones (P < 0.0422). IFN-gamma and IL-10 circulating levels were not affected by H. pylori presence, being not significantly different in the two groups.

Adult↗
PubMed2001

Increased 5-hydroxytryptamine-2 receptor binding in the frontal cortex of depressed patients responding to paroxetine treatment: a positron emission tomography scan study.

The changes in aminergic receptors elicited by antidepressant treatments have been extensively examined in the brain of experimental animals using radioligand and molecular techniques. However, there is a very limited direct information regarding the changes effected by such treatments in the human brain, as well as its relationship to clinical improvement. Using positron emission tomography (PET) scanning, the authors examined the cortical 5-Hydroxytryptamine-2A (5-HT2A) receptor binding of [18F]fluoro-ethyl-spiperone after a 4-week treatment with the selective serotonin reuptake inhibitor paroxetine. [18F]fluoro-ethyl-spiperone labels 5-HT2A receptors in the cortex and dopamine D2 receptors in the basal ganglia. A binding index (BI) was calculated in the frontal cortex and the basal ganglia (mostly caudate-putamen) by reference to cerebellum. Thirty-seven inpatients with major depression with a mean +/- SD score on the 21-item Hamilton Rating Scale for Depression (HAM-D-21) of 26.3 +/- 4.3 at admission were treated with paroxetine 40 mg/day. After 4 weeks of treatment, the BI in the frontal cortex of remitted patients (HAM-D-21 score = 4.7 +/- 4.0; N = 20) was significantly greater than the score in nonresponder patients (HAM-D-21 score = 21.2 +/- 4.0; N = 17) (BI = 0.54 +/- 0.15 and 0.41 +/- 0.17, respectively; p < 0.02). No such difference was observed in the basal ganglia (5.45 +/- 1.11 and 5.39 +/- 0.82, respectively; p = 0.85). The significant difference in cortical BI persisted when age was used as covariate (p < 0.016). These data suggest that clinical improvement in patients treated with paroxetine is associated with an increase in the density of 5-HT2A receptors in the frontal cortex.

Adult↗
PubMed2001

Acute effect of 3-(4-acetamido)-butyrril-lorazepam (DDS2700) on brain function assessed by PET at rest and during attentive tasks.

The aim of this study was to assess, by positron emission tomography (PET), the effect on cerebral functional activity of a new lorazepam-gamma-aminobutyric acid (GABA) conjugate [3-(4-acetamido)-butyrril lorazepam (DDS2700)]. Ten healthy volunteers were studied by PET and [18F]fluoro-deoxy-D-glucose ([18F]FDG) under baseline conditions and following the administration of DDS2700. Regional cerebral blood flow (rCBF) was measured by PET and 15O-water in three additional participants while they performed attentive tasks, before and after drug administration. DDS2700 induced a decrease in the regional cerebral metabolic rate of glucose (rCMRglu) in the thalamus (-17%), cerebellum (-11%) and caudate nucleus (-8%). The observed effects on glucose metabolism were probably related to the subjective sedation and tiredness reported by the participants. During the attentive tasks, rCBF increased in frontal and temporal regions associated with attentional processing of auditory material. These circuits were no longer active after DDS2700 administration, while rCBF increased in cingulate cortex, occipitoparietal regions, pons and cerebellum. These drug-induced activations might be directly related to intervening sleepiness and to the consequent effort in keeping attention focused on the tasks. The effects of DDS2700 on glucose metabolism at rest, and on rCBF during activation conditions, indicate a drug action on cerebral networks involved in alertness, vigilance and attention maintenance. PET assessment by [18F]FDG and water may provide complementary information in pharmacodynamic studies.

Adult↗
PubMed2001

Estrogens and colorectal cancer.

In recent years, several lines of epidemiologic, clinical and experimental evidences have been reported showing that estrogen hormones may be involved in malignant colorectal tumors. The sex differences in site-specific incidence, the increased incidence of colonic cancer in women with breast cancer, the protective effect of increasing parity and the reduced risk among women taking postmenopausal hormones, are all elements suggesting that sex hormones may play a role. Male rats experimentally exposed to the carcinogen dimethylhydrazine, have twice the risk of developing colon cancer and significantly shorter survival times than their female counterparts. Along with the clinical, experimental and epidemiologic findings there are also biologic reasons why estrogen may be protective. Most estrogen action appears to be exerted via the estrogen receptors (ERs) on target cells. ERs have been reported in several solid tumors including gastrointestinal neoplasms such as esophageal, gallbladder, gastric and colorectal cancer. At the end of 1995, a second ER (ER-beta) was cloned from the rat prostate cDNA library and subsequently, the human and mouse homologs. Its demonstration in normal and neoplastic human colorectal tissues and "in vitro" in colonic epithelial cells, has renewed interest in investigating the existence of two ER subtypes. The presence of two ERs could explain the selective actions of estrogens on different target tissues and, particularly, on the gastrointestinal tract. Finally, our studies suggest that estrogens and their receptors play an important role in the growth and progression of colorectal tumors, by interacting with other molecules required for cell proliferation like growth factors and polyamines.

Animals↗
PubMed2000

Brain serotonin1A receptor binding measured by positron emission tomography with [11C]WAY-100635: effects of depression and antidepressant treatment.

BACKGROUND: Pharmacological and postmortem investigations suggest that patients with major depressive disorder have alterations in function or density of brain serotonin1A (5-HT1A) receptors. The aim of the present study was to use positron emission tomography with the selective 5-HT1A receptor antagonist [11C]WAY-100635 to measure 5-HT1A receptor binding in depressed patients before and during treatment with selective serotonin reuptake inhibitors. METHODS: Positron emission tomographic scans with [11C]WAY-100635 were performed on 25 patients with major depressive disorder. These included 15 unmedicated depressed patients. Ten of these unmedicated patients were scanned again during selective serotonin reuptake inhibitor treatment. A further 10 patients with major depressive disorder were scanned on one occasion only while taking selective serotonin reuptake inhibitors. Comparisons were made with [11C]WAY-100635 positron emission tomographic scans in 18 healthy volunteer subjects. Region of interest analysis and statistical parametric mapping were performed on binding potential images generated using a reference tissue model. RESULTS: Binding potential values were reduced across many of the regions examined, including frontal, temporal, and limbic cortex in both unmedicated and medicated depressed patients compared with healthy volunteers. Binding potential values in medicated patients were similar to those in unmedicated patients. CONCLUSIONS: Major depressive disorder is associated with a widespread reduction in 5-HT1A receptor binding. This reduced 5-HT1A receptor binding was not changed by selective serotonin reuptake inhibitor treatment.

Adult↗
PubMed2000

Effects of fluvoxamine treatment on the in vivo binding of [F-18]FESP in drug naive depressed patients: a PET study.

This study investigates the effect of chronic treatment with Fluvoxamine, a potent and specific serotonin reuptake sites inhibitor (SSRI), on 5HT(2) serotonin and D(2) dopamine receptors in the brain of drug naive unipolar depressed patients. Drug effect was evaluated in different cortical areas and in the basal ganglia by positron emission tomography (PET) and fluoro-ethyl-spiperone ([(18)F]FESP), an high affinity 5HT(2) serotonin and D(2) dopamine receptors antagonist. Patients underwent a PET study at recruitment and after clinical response to Fluvoxamine treatment. Nine of the 15 patients recruited completed the study. Fluvoxamine treatment significantly improved clinical symptoms and modified [(18)F]FESP binding in the frontal and occipital cortex of all of the nine patients who completed the study; in these regions a mean 31% increase in the in vivo [(18)F]FESP binding was found (P < 0.01). On the contrary, no significant changes in the in vivo [(18)F]FESP binding were found in the basal ganglia where [(18)F]FESP binds mainly to D(2) dopamine receptors. Chronic treatment with Fluvoxamine significantly increases the in vivo binding of [(18)F]FESP in the frontal and occipital cortex of drug naive unipolar depressed patients. The increase of the in vivo binding of [(18)F]FESP may reflect a modification in 5HT(2) binding capacity secondary to changes in cortical serotonin activity.

Adult↗
PubMed2000

Epidermal growth factor and 17beta-estradiol effects on proliferation of a human gastric cancer cell line (AGS).

BACKGROUND: Recent evidence suggests that both estrogens and growth factors play an important role in the growth of gastrointestinal tumors. The expression of estrogen receptors (ER) and epidermal growth factor receptors (EGFR) in the gastrointestinal tract might therefore result in functional cross-talk between estrogens and EGF. The aim of the present study was to evaluate in vitro the effects of 17beta-estradiol and EGF administration on cell proliferation of a human gastric adenocarcinoma cell line (AGS) and investigate whether any interaction of these compounds may play a role in regulating gastric cancer cell proliferation. METHODS: Estrogen and EGFRs were detected by enzyme immunoassay. Cell proliferation was assessed with the MTT test. RESULTS: Exposure of AGS cells to increasing concentrations of 17beta-estradiol showed an anti-proliferative action at concentrations of 2 microM or higher. The addition of increasing concentrations of EGF stimulated cell growth, with a maximal response at 50 ng/ml EGF. The effect of increasing 17beta-estradiol concentrations combined with 50 ng/ml EGF was to increase cell growth at the lower estradiol concentrations. At the highest estradiol concentration the EGF proliferative effect was suppressed, and a decrease in proliferation rates occurred. Moreover, a significant negative correlation was found between 17beta-estradiol concentrations and EGFR expression. CONCLUSIONS: These findings suggest that growth of cultured gastric cancer cells (AGS) might be modulated by sex steroid hormones through interaction with EGF.

Adenocarcinoma↗
PubMed1999

Inhibitory effect of 17beta-estradiol on growth and the polyamine metabolism of a human gastric carcinoma cell line (HGC-27).

BACKGROUND: Estrogens may, by means of their receptors, modulate the growth of several tumors including gastrointestinal neoplasms. This control may occur through interaction with other molecules such as polyamines. An inverse relation between polyamine levels and the estrogen receptorial content has previously been demonstrated in vivo in human gastric carcinoma. The aim of the present study was to evaluate the effects of 17beta-Estradiol administration on the in vitro cell proliferation rates and the polyamine metabolism of an estrogen receptor-positive human gastric cancer cell line (HGC-27). METHODS: Estrogen receptors were detected with enzyme immunoassay. Cell proliferation was assessed by means of [3H]-thymidine incorporation and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test. The polyamine content was evaluated with high-performance liquid chromatography and the ornithine decarboxylase activity with a radiometric technique. RESULTS: Exposure of HGC-27 cells to increasing concentrations of 17beta-Estradiol showed that an antiproliferative action became evident at concentrations of 8 microM or higher. At such concentrations, ornithine decarboxylase (ODC) activity was also significantly reduced, as were all polyamine levels, compared with the untreated control. These findings suggest that one of the mechanisms underlying 17beta-Estradiol inhibition of HGC-27 cell proliferation is a decrease in ODC activity and, hence, in polyamine production.

Cell Division↗
PubMed1999

Central nervous system involvement in systemic lupus erythematosus patients without overt neuropsychiatric manifestations.

OBJECTIVE: To verify whether features of CNS involvement can be detected in SLE patients without overt neuropsychiatric manifestations. METHODS: 114 SLE patients who had never received a diagnosis of neuropsychiatric lupus (never-NPSLE) were studied and compared to 65 SLE patients with known neuropsychiatric involvement (NPSLE). The study relied on evaluation of neurocognitive functions by means of a battery of neuropsychological tests, on psychiatric and neuropsychological assessments and on neuroimaging studies (computed tomography, magnetic resonance, single photon emission computed tomography (SPECT)). RESULTS: Clinical features, including disease duration/activity and pharmacological therapy, of never-NPSLE and NPSLE patients were similar. Short-term and long-term memory, visuo-spatial and verbal information processing were similarly compromised in never-NPSLE and in NPSLE patients; only attention was significantly more compromised in NPSLE patients. Psychiatric morbidity was higher than expected in never-NPSLE patients, although less than in the control neuropsychiatric group. Ischemic lesions, multiple small high intensity lesions and cortical atrophy, detected by CT and MR scans, as well as abnormal SPECT were also frequently detected in never-NPSLE patients. Interestingly, left parietal and occipital area hypoperfusion by SPECT was significantly more frequent in the patients with impaired visuo-spatial intelligence and short-term memory. CONCLUSIONS: Most abnormalities detected by available diagnostic tools and characteristics of neuropsychiatric SLE are also present in non-symptomatic patients. They may derive from an unexpected widespread involvement of the CNS and are not per se sufficient, in the absence of clinical manifestations, for a diagnosis of neuropsychiatric SLE.

Adult↗
PubMed1999

Helicobacter pylori infection and host cell responses.

It is well known that Helicobacter pylori is able to colonize the gastric mucosa, causing a chronic and persistent infection with complications, such as peptic ulcer and gastric cancer. This review places emphasis on some epidemiological aspects of Helicobacter pylori infection and its mode of transmission. At the same time, invasive and non-invasive methods of diagnosis of Helicobacter pylori infection are illustrated. More space is devoted to the host response following invasion of the stomach. In this respect, the role played by different growth factors and polyamines in the course of Helicobacter pylori disease is discussed also in relation to the result of eradicating treatment. On the other hand, an accurate description of the host immune responses against Helicobacter pylori organism and/or their components (e.g. lipopolysaccharides) is reported. Finally, since Helicobacter pylori has been classified as a class I carcinogen, current researches are focussed on the Helicobacter pylori-induced carcinogenesis.

Animals↗
PubMed1999

FDG/PET and spiral CT image fusion for medistinal lymph node assessment of non-small cell lung cancer patients.

BACKGROUND: To assess the potential usefulness of 18F-FDG/PET and spiral-CT images concurrent assessment and coregistration in staging mediastinal lymph node involvement in patients with non small cell lung cancer. METHODS: 28 patients waiting to undergo surgical treatment underwent spiral-CT and PET examinations on the same day. The results of the two studies were interpreted separately, together (CT&PET) and following their fusion in a single image (CT+PET). Results of spiral-CT, PET, CT&PET and CT+PET were assessed with respect to the histological diagnosis. RESULTS: A correct assessment of mediastinal lymph nodes was achieved by spiral-CT in 21 of the 28 patients, in 22 of the 28 patients by PET, in 24 patients by CT&PET and in 25 patients by CT+PET. CONCLUSIONS: CT+PET is more accurate than spiral-CT and PET alone in staging mediastinal lymph node involvement in lung cancer patients, with possible implications for their prognosis and therapy.

Aged↗
PubMed1998

Differential distribution of striatal [123I]beta-CIT in Parkinson's disease and progressive supranuclear palsy, evaluated with single-photon emission tomography.

Functional imaging of the presynaptic dopaminergic activity using single-photon emission tomography (SPET) and iodine-123 labelled 2-beta-carboxymethoxy-3-beta-(4-iodophenyl)tropane ([123I]beta-CIT) is important for the assessment of disease severity and progression in patients with Parkinson's disease (PD). However, its capability to discriminate between different extrapyramidal disorders has not yet been assessed. The aim of this study was to evaluate the possibility of differentiating patients with PD and with progressive supranuclear palsy (PSP) by means of this method. The distribution of [123I]beta-CIT in the basal ganglia was assessed in six normal subjects, 13 petients with PD and five patients with PSP in whom the disease was mild. SPET images were obtained 24+/-2 h after i.v. injection of the tracer using a brain-dedicated system (CERASPECT). MR and SPET images were co-registered in four normal subjects and used to define a standard set of 16 circular regions of interest (ROIs) on the slice showing the highest striatal activity. The basal ganglia ROIs corresponded to (1) the head of caudate, (2) a region of transition between the head of caudate and the anterior putamen, (3) the anterior putamen and (4) the posterior putamen. A ratio of specific to non-displaceable striatal uptake was calculated normalising the activity of the basal ganglia ROIs to that of the occipital cortex (V3"). ANOVA revealed a global reduction of V3" in all ROIs of PD and PSP patients compared with normal controls (P<0. 0001). A Mann-Whitney U test showed that the difference between PD and PSP patients was statistically significant for the caudate region only (Z value: 2.6; P<0.01). By subtracting V3" caudate values from those of the putamen, differentiation from PSP was possible in 10/13 PD patients. In conclusion, analysis of [123I]beta-CIT distribution in discrete striatal areas provides information on the relative caudate-putamen damage, with different values being obtained in patients clinically diagnosed as having either PD or PSP.

Aged↗
PubMed1998

The influence of Helicobacter pylori eradication on the gastric mucosal content of epidermal growth factor, transforming growth factor-alpha, and their common receptor.

BACKGROUND: The relationship between the expression of epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) and that of their receptor (EGF-R) in the Helicobacter pylori-infected gastric mucosa has not been completely elucidated. The aim of this study was to examine the interplay between H. pylori colonization and gastric mucosal growth factor content. METHODS: By means of a solid-phase enzyme-linked immunosorbent assay EGF, TGF-alpha, and EGF-R levels and interleukin-1beta (IL-1beta) content, which is considered a marker of chronic inflammation, were evaluated in the antral mucosa of 24 H. pylori-positive patients before and 8 weeks after eradication therapy. RESULTS: After therapy H. pylori was eradicated in 19 patients. The eradication was accompanied by a significant decrease in IL-1beta content and an increase in EGF and TGF-alpha levels. On the other hand, in the five patients in whom the bacterium was not eradicated EGF, TGF-alpha, and EGF-R levels were quite similar to those assayed before therapy, whereas IL-1beta content was still high. CONCLUSIONS: These results suggest that H. pylori exerts an inhibitory effect on the mucosal expression of EGF and TGF-alpha, which are likely involved in the gastric mucosa repair process.

Adult↗
PubMed1998

EGF, TGF-alpha, and EGF-R in human colorectal adenocarcinoma.

The over-expression of epidermal growth factor receptor (EGF-R), EGF and transforming growth factor alpha (TGFalpha) could be a mechanism for colorectal tumor cells to escape normal growth controls. Our aims were: (i) to evaluate EGF, TGFalpha, and EGF-R concentrations in neoplastic tissue and surrounding mucosa from 40 patients with colorectal adenocarcinoma, and (ii) to assess the expression of these growth factors and their receptor in relation to the tumor site. EGF, TGFalpha, and EGF-R were detected in either colorectal neoplastic tissue or surrounding mucosa. Significantly increased levels of EGF and EGF-R were present in neoplastic samples compared to surrounding mucosa. Furthermore, a significant increase in TGFalpha and in EGF levels was observed in the left-sided surrounding mucosa and left-sided neoplastic tissue, respectively. EGF-R stimulation by its ligands may play an important role in colorectal neoplastic tissue. Moreover, the higher content of growth factors in the left-side than the right-side colon suggests different growth properties in the proximal and distal colon.

Adenocarcinoma↗
PubMed1997

Whole-body scintigraphy with 99Tcm-MIBI, 18F-FDG and 131I in patients with metastatic thyroid carcinoma.

We assessed the relative usefulness of whole-body planar scintigraphy with 99Tcm-methoxyisobutyl isonitrile (99Tcm-MIBI), 2-[18F]fluoro-2-deoxy-D-glucose (18F-FDG-RS) rectilinear scanning and with diagnostic and therapeutic doses of 131I, for the detection of local recurrences and metastatic lesions in 12 patients with thyroid carcinoma and elevated thyroglobulin serum levels. All images were evaluated independently by three experienced observers to define the number and location of metastatic lesions. 18F-FDG-RS and 99Tcm-MIBI scintigraphy provided similar results, but the tracer that allowed the detection of the highest number of metastases was 99Tcm-MIBI. Both 99Tcm-MIBI scintigraphy and 18F-FDG-RS appear to be more sensitive than 131I scintigraphy for the detection of metastases of thyroid carcinoma. Tomographic acquisitions were also performed on a limited field of view in each subject and, as expected, 18F-FDG-PET was more sensitive than 18F-FDG-RS. 99Tcm-MIBI scintigraphy, a widely available and relatively non-expensive technique, therefore sems suitable for the assessment and follow-up of patients with metastatic thyroid carcinoma and does not require the withdrawal of hormone therapy for lesion imaging.

Adenocarcinoma, Follicular↗
PubMed1997

Diagnostic accuracy and predictive value of 201T1 SPET for the differential diagnosis of cerebral lesions in AIDS patients.

The use of 201T1 has been proposed for the differential diagnosis of lymphomas and non-neoplastic brain masses in AIDS patients. The aim of this study was to assess the diagnostic accuracy of three different semi-quantitative methods for the analysis of 201T1 SPET brain images in individuals with AIDS and brain lesions. Thirty-seven AIDS patients with contrast-enhancing brain lesions underwent 201T1 SPET. Three different lesion-to-background uptake indices were calculated: (1) small lesion/large background (SL/LB; i.e. counts in a 3 x 3 pixel ROI in the lesion/counts in a 7 x 7 pixel ROI in the contralateral healthy hemisphere); (2) small lesion/multiple small background (SL/MSL; i.e. counts in a 3 x 3 pixel ROI in the lesion/average counts of ten 3 x 3 ROIs over the highest background pixel values); (3) large lesion/large background (LL/LB; i.e. counts in an elliptic ROI in the lesion/counts in a contralateral mirrored ROI). Data analysis included a ROC curve analysis to identify the cut-off value corresponding to the highest accuracy value, and an analysis of the predictive value to classify the patients in three categories (high, intermediate and low risk of lymphoma). The greatest accuracy (71%) was achieved with the LL/LB method of analysis. Using this method, 62% of patients could be classified as either having lymphoma or not, whereas 38% could not be classified. LL/LB values > or = 2.9 are suggestive of the presence of lymphomas, whereas values < or = 2 are highly predictive of the presence of a lesion other than lymphoma. However, LL/LB values between 2 and 3 are not diagnostic and adjunctive tests should be carried out. In conclusion, 201T1 SPET was an adequate diagnostic tool in approximately 70% of the cases in this study.

AIDS-Related Opportunistic Infections↗