Efficacy of photobiomodulation in the management of tinnitus: A systematic review of randomized control trials.

There is a controversy in regards to the efficacy of photobiomodulation (PBM) in the management of tinnitus. The aim was to systematically review randomized controlled trials (RCTs) that assessed the efficacy of PBM (low-level laser therapy) in the management of tinnitus. The focused question was "Is PBM effective in the management of tinnitus?". Indexed databases were searched up to and including June 2020 using different combinations of the following key words: (a) laser; (b) diode; (c) low-level laser therapy; (d) photobiomodulation; (e) tinnitus; (f) medium-level laser; (g) photo-biomodulation; and (h) low-power laser; and RCTs performed on humans were included. Letters to the editor; case reports/series; commentaries; experimental studies and historic reviews were excluded. The risk of bias was assessed using the modified cochrane collaboration tool. The format of the current systematic review was personalized to summarize the appropriate information. Ten RCTs (2 single-blinded and 8 double-blinded) were included. One study reported 30% and 100% resolution of tinnitus using diode and Neodymium-doped Yttrium Aluminum Garnet lasers; respectively. One study reported that PBM was effective in relieving tinnitus for up to 3 months. Eight studies reported that PBM was ineffective in the management of chronic tinnitus. The risk of bias was high; medium and low in 4; 5 and 1 studies; respectively. The effectiveness of PBM in the management of tinnitus remains debatable. Further power-adjusted and well-designed RCTs with long-term follow-up are needed.

Outcome of orthodontic palatal plate therapy for orofacial dysfunction in children with Down syndrome: A systematic review.

To evaluate the effects of orthodontic palatal plate therapy (OPPT) in the treatment of orofacial dysfunction in children with Down syndrome (DS). Indexed databases were searched. Clinical trials in DS allocated to test (treatment with palatal plates) versus control group (without palatal plates/special physiotherapy for orofacial stimulation) with follow-up of any time duration and assessing mouth closure, tongue position, active and inactive muscle function as outcomes. Study designs, subject demographics, frequency and duration of palatal plate therapy, method for assessment, follow-up period and outcomes were reported according to the PRISMA guidelines. Eight clinical studies were included. The risk of bias was considered high in three studies and moderate in 5 studies. The number of children with DS ranged between 9 and 42. The mean age of children with DS at the start of the study ranged between 2 months and 12 years. The duration of palatal plate therapy ranged between 4 months and 48 months. The follow-up period in all studies ranged from 12 to 58 months. All studies reported OPPT to be effective in improving orofacial disorders in children with DS. Most of the included studies suggest that palatal plate therapy in combination with physiotherapy/orofacial regulation therapy according to Castillo Morales/speech and language intervention seems to be effective in improving orofacial disorders in children with DS. However, the risk of bias of the included studies was high to moderate. Longitudinal trials with standardized evaluation methods, age of children at treatment initiation, treatment duration and standard orofacial outcomes are recommended.

Treating Cryptosporidium parvum infection in calves.

The present study evaluated the therapeutic efficacy of azithromycin, co-trimoxazole and kalvangi (Nigella sativa, also known as Black Cumin) against Cryptosporidium parvum infection in calves under field conditions. The experimental calves were treated with azithromycin (group A) at 1500 mg/calf/day, co-trimoxazole (group B) at 30 mg Kg-1 and kalvangi seeds powder (group C) at 750 mg Kg-1 BW orally for 7 days. Calves in the group D were naturally infected with C. parvum , untreated animals (positive control) while the calves in the group E were uninfected negative control animals. A significant decrease (p < 0.05) in oocyst counts for calves in groups A, B and C was observed compared to group D. When the oocyst counts amongst the treatment groups A, B and C were compared, a significant decrease (p < 0.05) was observed in group A. On day 21 post-treatment, the efficacy of azithromycin, co-trimoxazole and kalvangi in calves was 88.2% (95% C.I. ± 15.4), 45% (95% C.I. ± 21.8) and 27.8% (95% C.I. ± 20.7), respectively. This study confirmed previous reports of azithromycin efficacy against C. parvum infection, but found co-trimoxazole and kalvangi to be ineffective for this infection under these treatment regimens.

Iatrogenic perforation at colonic imaging.

AIM: Adequate colonic imaging is generally an invasive procedure with attendant risks, particularly perforation. Endoscopy, barium enema and computed tomographic colonography (CTC) are the main techniques for investigating patients with symptoms of, or screening for, colorectal cancer. The potential complications of these investigations have to be weighed against the benefits. This article reviews the literature on the incidence, presentation and management of iatrogenic colonic perforation at colonic imaging. METHOD: A literature review of relevant studies was undertaken using PubMed, Cochrane library and personal archives of references. Manual cross-referencing was performed, and relevant references from selected articles were reviewed. Studies reporting complications of endoscopy, barium enema and CT colonography were included in this review. RESULTS: Twenty-four studies were identified comprising 640,433 colonoscopies, with iatrogenic perforation recorded in 585 patients (0.06%). The reported perforation rate with double-contrast barium enema was between 0.02 and 0.24%. Serious complications with CTC were infrequent, though nine perforations were reported in a case series of 24,365 patients (0.036%) undergoing CTC. CONCLUSION: Perforation remains an infrequent and almost certainly under-reported, complication of all colonic imaging modalities. Risk awareness, early diagnosis and active management of iatrogenic perforation minimizes an adverse outcome.

Fluctuations in number of Cercospora beticola conidia in relationship to environment and disease severity in sugar beet.

Cercospora leaf spot, caused by Cercospora beticola, is the most damaging foliar disease of sugar beet in Minnesota (MN) and North Dakota (ND). Research was conducted to characterize the temporal progression of aerial concentration of C. beticola conidia in association with the environment and disease severity in sugar beet. In 2003 and 2004, volumetric spore traps were placed within inoculated sugar beet plots to determine daily dispersal of conidia at Breckenridge, MN, and St. Thomas, ND. Plots were rated weekly for disease severity. At both locations, conidia were first collected in early July 2003 and late June in 2004. Peaks of conidia per cubic meter of air were observed with maxima in late August 2003 and in early September 2004 at both locations. Peaks of airborne conidium concentration were significantly correlated with the average temperature of daily hours when relative humidity was greater than 87%. Weekly mean hourly conidia per cubic meter of air was significantly (P < 0.01) associated with disease severity during both years and across locations. This study showed that C. beticola conidial numbers may be used to estimate potential disease severity that, with further research, could be incorporated in a disease forecasting model to rationalize Cercospora leaf spot management.

Accuracy of choroidal melanoma diagnosis by general ophthalmologists: a prospective study.

PURPOSE: To estimate the proportion of 'false positives' in patients referred with a diagnosis of suspected choroidal melanoma by general ophthalmologists to an ocular oncology centre. METHODS: A prospective study of patients referred by general ophthalmologists to an ocular oncology centre was undertaken over a 14-week period. The diagnosis was made clinically in patients receiving radiotherapy or phototherapy and was confirmed by histopathology in patients requiring fine needle aspiration biopsy (FNAB) or enucleation. RESULTS: A total of 132 new patients were seen in 10 consecutive ocular oncology clinics between 29 March 2004 and 5 July 2004. The mean age was 62 years (range 28-88 years) and 60 (55%) were female. Among the 83 suspected malignant posterior segment lesions, the suspected diagnosis included choroidal melanoma (73), choroidal metastasis (6), 'choroidal tumour' (3), and 'Solid retinal detachment' (1). Only 50 of the 73 suspected melanomas were confirmed (68.5%; 95% CI, 57-78%), the oncologist's diagnosis in the remaining 23 being choroidal naevus (10), choroidal metastasis (1), circumscribed choroidal haemangioma (2) and others (10). Only one of six patients with suspected metastases had this condition, the remainder having melanoma (1), lymphoma (1), circumscribed choroidal haemangioma (1), and others (2). The 'choroidal tumours' and 'solid detachments' were found to be chorio-retinal disciform scar (1), varix of vortex vein (1), eccentric CNV (1), and subretinal haemorrhage (1) CONCLUSION: Approximately 30% of patients referred to an ocular oncology service with the diagnosis of choroidal melanoma have an incorrect diagnosis.

Invasive aspergillosis with polyarthritis.

We report a case of septic arthritis of multiple joints in an 18-year-old male caused by Aspergillus fumigatus. His initial presentation was of low-grade fever followed by involvement of both knee and ankle joints. Later, there was also involvement of metacarpophalangeal joints. Diagnosis was based on biopsy and culture of the skin and joint lesions. The symptoms resolved readily under administration of itraconazole. We recommend that clinicians should be alerted of potential fungal etiology in cases of fever and chronic arthritis, which is unresponsive to conventional medical therapy.

In vitro and in vivo activities of syn2836, syn2869, syn2903, and syn2921: new series of triazole antifungal agents.

The in vitro and in vivo activities of four azole compounds belonging to a new series of 2(2,4-difluorophenyl)-3-(4-substituted piperazin-1-yl)-1-(1,2,4-triazol-1-yl) butanol antifungal agents is described. The compounds were selected from a library of azole compounds synthesized by our group. The in vitro activities of Syn2869, Syn2836, Syn2903, and Syn2921 against a panel of over 240 recently collected clinical isolates of yeast and molds were determined, and the results were compared with those obtained with fluconazole (FLC), itraconazole (ITC), and amphotericin B (AMB). The MICs at which 90% of the isolates were inhibited (MIC(90)s) for the four test compounds for strains of Candida spp. ranged from <0.048 to 0.78 microg/ml. All compounds were also active against FLC-resistant Candida albicans and other Candida sp. strains. Moreover, MIC(90)s for strains of Cryptococcus neoformans, Aspergillus spp., Trichophyton spp., and Microsporum spp. were also low and ranged from <0.048 to 0.39 microg/ml. The test compounds produced a fungistatic pattern during the time-kill kinetic studies. In vivo studies indicated that all four test compounds have good efficacies against C. albicans in a murine systemic infection model and significantly improved the survival rates of the infected mice. The results for Syn2903 were similar to those for FLC, while the other compounds were slightly less effective but had ranges of activities similar to the range of activity of ITC. The compounds were also evaluated against an Aspergillus fumigatus systemic infection. Syn2903 was also superior to ITC, whereas the efficacy data for the other compounds were similar to those for ITC. It was concluded from the data generated for this new series of azole compounds in the studies described above that further pharmacokinetic and toxicologic evaluations are warranted prior to selection of a candidate compound for preclinical testing.

Doubly homologated dihalovinyl and acetylene analogues of adenosine: synthesis, interaction with S-adenosyl-L-homocysteine hydrolase, and antiviral and cytostatic effects.

Treatment of the 6-aldehyde derived by Moffatt oxidation of 3-O-benzoyl-1,2-O-isopropylidene-alpha-D-ribo-hexofuranose (2c) with the dibromo- or bromofluoromethylene Wittig reagents generated in situ with tetrabromomethane or tribromofluoromethane, triphenylphosphine, and zinc gave the dihalomethyleneheptofuranose analogues 3b and 3d, respectively. Acetolysis, coupling with adenine, and deprotection gave 9-(7,7-dibromo-5,6, 7-trideoxy-beta-D-ribo-hept-6-enofuranosyl)adenine (5a) or its bromofluoro analogue 5b. Treatment of 5a with excess butyllithium provided the acetylenic derivative 9-(5,6, 7-trideoxy-beta-D-ribo-hept-6-ynofuranosyl)adenine (6). The doubly homologated vinyl halides 5a and 5b and acetylenic 6 adenine nucleosides were designed as putative substrates of the "hydrolytic activity" of S-adenosyl-L-homocysteine (AdoHcy) hydrolase. Incubation of AdoHcy hydrolase with 5a, 5b, and 6 resulted in time- and concentration-dependent inactivation of the enzyme (K(i): 8.5 +/- 0.5, 17 +/- 2, and 8.6 +/- 0.5 microM, respectively), as well as partial reduction of enzyme-bound NAD(+) to E-NADH. However, no products of the "hydrolytic activity" were observed indicating these compounds are type I mechanism-based inhibitors. The compounds displayed minimal antiviral and cytostatic activity, except for 6, against vaccinia virus and vesicular stomatitis virus (IC(50): 15 and 7 microM, respectively). These viruses typically fall within the activity spectrum of AdoHcy hydrolase inhibitors.

Nitric oxide synthase inhibitor attenuates intestinal damage induced by zinc deficiency in rats.

A nitric oxide synthase (NOS) inhibitor, NG-nitro-L -arginine methyl ester (L-NAME), was given to zinc-deficient (ZD) rats to determine whether it prevents the intestinal damage usually observed under these conditions. Weanling male rats were given free access to a ZD diet (2 mg zinc/kg), whereas control rats including pair-fed (PF) and ad libitum consumption (AL) groups were given a zinc-supplemented (50.8 mg zinc/kg) diet for 4 wk. Half of the ZD rats received L-NAME (0.3 g/L in drinking water) for 3 wk starting at the wk 2 of the deficient period. Plasma zinc concentration in ZD rats was significantly lower (P < 0.05) than that of AL and PF rats. Administration of L-NAME did not alter this concentration. Intestinal zinc concentration did not differ among groups. However, metallothionein-1 (MT-1) mRNA level was significantly lower in the intestine of ZD rats than in AL or PF rats. Treatment of ZD rats with L-NAME did not affect this level. Intestinal microvascular permeability evaluated by Evans blue showed significantly higher extravasation in ZD rats than in AL rats, whereas L-NAME administration inhibited the extravasation. Expression of inducible NOS mRNA was observed in intestine of ZD but not of AL or PF rats, and there was no significant difference between ZD rats, regardless of L-NAME treatment. The activity ratio of inducible NOS to total NOS in ZD rats not receiving L-NAME was significantly higher than that in AL rats or ZD rats treated with L-NAME (P < 0.05). The number of apoptotic-positive and goblet cells in intestinal villi was significantly higher in ZD rats compared with AL or PF rats. L-NAME administration in ZD rats reversed this effect. These results indicate that inhibition of NOS ameliorates zinc deficiency-induced intestinal damage in rats.

Alanyl-glutamine-supplemented parenteral nutrition increases luminal mucus gel and decreases permeability in the rat small intestine.

BACKGROUND: Effect of supplemental alanyl-glutamine in standard TPN (S-TPN) on luminal mucus gel and small intestinal permeability was investigated. METHODS: Thirty Sprague-Dawley rats were divided into group I (n = 10), receiving standard rat diet; group II (n = 10), receiving S-TPN; and group III (n = 10), receiving alanyl-glutamine-supplemented TPN for 1 week. After 1 week, fluorescein isothiocyanate (FITC)-dextran was injected into the small intestine of the rats, and they were killed. A small intestinal sample and portal blood were obtained for morphologic and functional analysis of mucus gel and intestinal permeability. RESULTS: In group II, thickness and optical density of mucus gel per millimeter serosal length of intestine were significantly lower than group I (p<.001) and were significantly higher in group III than in group II (p<.001). The number of goblet cells in the villi and in the crypt of the small intestine was significantly lower in group II than in group I (p<.001) and was significantly higher in group III than in group II (p<.001), with the exception of the villi of jejunum. Villous and crypt surface area per millimeter serosal length of intestine was significantly lower in group II than in group I (p<.001) and was significantly higher in group III than in group II (p<.001). Small intestinal permeability to FITC-dextran was significantly higher in group II than in group I (p<.001) and was significantly lower in group III than in group II (p<.001). Glucosamine synthetase level was significantly higher in group III than in group I and ileum of group II (p<.001). CONCLUSIONS: Alanyl-glutamine-supplemented TPN prevents a decrease in mucus gel and an increase in small intestinal permeability associated with S-TPN.

Zinc deficiency enhances interleukin-1alpha-induced metallothionein-1 expression in rats.

This study investigated whether interleukin-1alpha-induced metallothionein gene expression is affected by zinc deficiency. Weaning male rats were fed a zinc-deficient (ZD) diet (2 mg zinc/kg) or a zinc-supplemented diet [50.8 mg zinc/kg; controls for the diet included pair-fed (PF) and ad libitum consumption groups (AL)] for 4 wk. All rats except those that served as controls for interleukin-1alpha administration, (injected with vehicle and killed at 0 h) were then injected subcutaneously with interleukin-1alpha (2 x 10(7) units/kg body wt) and killed at 3, 6, 12, 24 and 72 h after the injection. Compared with AL and/or PF rats, zinc depletion significantly reduced zinc concentrations in plasma and liver but not in kidney or intestine, and significantly reduced hepatic, renal, and intestinal metallothionein-1 mRNA levels analyzed by competitive reverse transcription-polymerase chain reaction (RT-PCR). Interleukin-1alpha injection reduced plasma zinc concentration and enhanced liver zinc concentration, but did not affect zinc levels in kidney or intestine. Metallothionein-1 mRNA was significantly elevated by interleukin-1alpha in liver, kidney and intestine of all groups; the levels in liver and kidney of ZD rats 6 h after the injection were significantly higher than those of AL or PF rats. Liver metallothionein protein levels were enhanced after interleukin-1alpha injection in both AL and ZD rats. Semiquantitative RT-PCR revealed significantly higher hepatic levels of interleukin-1 receptor type-I mRNA in ZD rats than in AL and PF rats but no differences in renal or intestinal tissues among groups before interleukin-1alpha challenge. In conclusion, zinc deficiency induces upregulation of metallothionein-1 gene expression in response to interleukin-1alpha challenge in rats.

Induction of nitric oxide synthase in rat intestine by interleukin-1alpha may explain diarrhea associated with zinc deficiency.

Synthesis of inducible nitric oxide synthase (iNOS) in the intestine may result in local tissue damage. We investigated whether a challenge with interleukin-1alpha could give rise to intestinal iNOS expression and diarrhea in rats of differing zinc status. Weaning male rats were fed a zinc-deficient (ZD) diet (2 mg zinc/kg) for 4 wk to induce zinc deficiency or a zinc-supplemented diet [50.8 mg zinc/kg; controls, including pair-fed (PF ) and ad libitum (AL) consumption groups], and then subcutaneously injected with interleukin-1alpha (2 x 10(7) units/kg body wt). Without the interleukin-1alpha challenge, ZD rats had significantly lower plasma zinc concentration than the other groups. Intestinal metallothionein-1 mRNA abundance was lower in ZD rats than in AL rats. iNOS was expressed in the intestine of ZD rats but not in the others. None of the rats experienced diarrhea during the feeding period. Interleukin-1alpha led to a reduction in plasma zinc concentration, enhancement in intestinal metallothionein-1 mRNA levels, and expression of the intestinal iNOS gene in all groups. However, the abundance of iNOS mRNA was significantly higher in ZD rats than in the other groups. The presence of iNOS protein was demonstrated by immunohistochemical staining in the intestine of ZD rats that had been treated with interleukin-1alpha 12 h earlier. In addition, diarrhea occurred in most of the ZD rats and some of the PF rats but not in AL rats after interleukin-1alpha treatment. We conclude that ZD rats respond to interleukin-1alpha challenge more severely than controls, reflected by a more marked and prolonged iNOS expression and a greater incidence of diarrhea.

Adhesive mucous gel layer and mucus release as intestinal barrier in rats.

BACKGROUND: Although it has been reported that total parenteral nutrition induces an increased intestinal permeability and a decreased mucous gel layer covering the intestinal epithelium, the role of mucous gel on intestinal permeability has not been well understood. We examined the in vivo effects of N-acetyl cysteine (NAC) as mucolytic agent and colchicine as suppressant of the mucus production on the intestinal transmission of fluorescein isothiocyanate dextran 70,000 (FITC-dextran). METHODS: Rats were divided into four groups. In each group, FITC-dextran (750 mg/kg) with or without NAC (3000 mg/kg) was injected into the small intestinal lumen 3 hours after intraperitoneal injection of saline or colchicine (Col, 10 mg/kg). Thirty minutes after injection of FITC-dextran, blood samples were taken from portal vein to analyze plasma fluorescein concentration by fluorescence spectrometry. Samples of small intestine were sectioned in a cryostat for fluorescence microscopy, and the identical sections were stained by periodic acid-Schiff reaction. RESULTS: Plasma FITC-dextran level in NAC group was higher than that in control group (p < .01), that in Col + NAC group was higher than that in Col group (p < .01) and that in Col + NAC group was higher than that in NAC group (p < .05). The spaces between villi were filled with mucous gel in the control and Col groups, whereas those were not entirely filled with mucous gel in NAC and Col + NAC groups. FITC-dextran and mucous gel showed complementary distribution in all rats. The villous interstitial edema was recognized in NAC group and the villi were disrupted in Col + NAC group. CONCLUSIONS: These results suggest that intestinal permeability is possibly affected not only by the mucous gel covering the intestinal epithelium but also by mucus release from goblet cells of the small intestine.

Inhibitory and excitatory amino acids in cerebrospinal fluid of neurolathyrism patients, a highly prevalent motorneurone disease.

Neurolathyrism is caused by overconsumption of seeds containing 3-N-oxalyl-L-2,3-diaminopropanoic acid (beta-ODAP). Amino acids levels of cerebrospinal fluid (CSF) were studied in 50 patients with neurolathyrism and 12 healthy volunteers. The levels of excitatory amino acids glutamate and aspartate were 281% and 71% respectively of control values. The concentration of inhibitory amino acids glycine and taurine were 277% and 198% respectively of the levels in CSF from control individuals. There was a significant correlation between the level of glycine and the duration of the disease. We also found increased levels of threonine, serine and alanine. In contrast to reports on other motor neurone diseases where an increase of isoleucine was observed we found a significant decrease of isoleucine. The results suggest a disturbance of amino acid metabolism due to excitotoxic damages caused by beta-ODAP, a dietary excitatory amino acid.

Nasal or oral oil application on infants: a possible risk factor for adult bronchiectasis.

Lipid pneumonia has been observed in infants exposed by inhalation of oil or butter applied into the nose or throat as part of an old custom. We performed a case-control study to test the hypothesis, that this ancient tradition may be a predisposing factor to bronchiectasis. A case group of 59 patients with bronchiectasis and three control groups -46 patients with COPD, 32 asthmatics, and 71 healthy Saudis-were questioned about possible risk factors of bronchiectasis including nasal or oral application of oil/butter at infancy. The risk of witnessed exposure to this old folk remedy was significantly higher among the cases than the controls (OR = 3.9 (1.7-8.8), (95% confidence interval) p < 0.001). Application of oil or butter into the nasal or oral cavity of infants may be a risk factor for bronchiectasis.

From soil to brain: zinc deficiency increases the neurotoxicity of Lathyrus sativus and may affect the susceptibility for the motorneurone disease neurolathyrism.

Zinc deficiency and oversupply of iron to the roots of grass pea (Lathyrus sativus) induce increases in the content of the neurotoxin beta-L-ODAP (3-oxalyl-L-2,3-diaminopropanoic acid) in the ripe seeds. The transport of zinc to the shoots is enhanced by the addition of beta-L-ODAP. The neurotoxin of L. sativus is proposed to function as a carrier molecule for zinc ions. Soils, depleted in micronutrients from flooding by monsoon rains (Indian subcontinent) or otherwise poor in available zinc and with high iron content (Ethiopian vertisols), may be responsible for higher incidence of human lathyrism, one of the oldest neurotoxic diseases known to man. A role for brain zinc deficiency in the susceptibility for lathyrism is postulated.