Discovery of sulfonamide resistance genes in deep groundwater below Patna, India.

Global usage of pharmaceuticals has led to the proliferation of bacteria that are resistant to antimicrobial treatments, creating a substantial public health challenge. Here, we investigate the emergence of sulfonamide resistance genes in groundwater and surface water in Patna, a rapidly developing city in Bihar, India. We report the first quantification of three sulfonamide resistance genes (sulI, sulII and sulIII) in groundwater (12-107 m in depth) in India. The mean relative abundance of gene copies was found to be sulI (2.4 × 10-2 copies/16S rRNA gene) > sulII (5.4 × 10-3 copies/16S rRNA gene) > sulIII (2.4 × 10-3 copies/16S rRNA gene) in groundwater (n = 15) and surface water (n = 3). A comparison between antimicrobial resistance (AMR) genes and wastewater indicators, particularly tryptophan:fulvic-like fluorescence, suggests that wastewater was associated with AMR gene prevalence. Urban drainage channels, containing hospital and domestic wastes, are likely a substantial source of antimicrobial resistance in groundwater and surface water, including the Ganges (Ganga) River. This study is a reference point for decision-makers in the fight against antimicrobial resistance because it quantifies and determines potential sources of AMR genes in Indian groundwater.

Spatial and seasonal controls on dissolved organic matter composition in shallow aquifers under the rapidly developing city of Patna, India.

The distribution and composition of dissolved organic matter (DOM) affects numerous (bio)geochemical processes in environmental matrices including groundwater. This study reports the spatial and seasonal controls on the distribution of groundwater DOM under the rapidly developing city of Patna, Bihar (India). Major DOM constituents were determined from river and groundwater samples taken in both pre- and post-monsoon seasons in 2019, using excitation-emission matrix (EEM) fluorescence spectroscopy. We compared aqueous fluorescent DOM (fDOM) composition to satellite-derived land use data across the field area, testing the hypothesis that the composition of groundwater DOM, and particularly the components associated with surface-derived ingress, may be controlled, in part, by land use. In the pre-monsoon season, the prominence of tryptophan-like components likely generated from recent biological activity overwhelmed the humic-like and tyrosine-like fluorescence signals. Evidence from fluorescence data suggest groundwater in the post-monsoon season is composed of predominantly i) plant-derived matter and ii) anthropogenically influenced DOM (e.g. tryptophan-like components). Organic tracers, as well as Eh and Cl-, suggest monsoonal events mobilise surface-derived material from the unsaturated zone, causing dissolved organic carbon (DOC) of more microbial nature to infiltrate to >100 m depth. A correlation between higher protein:humic-like fluorescence and lower vegetation index (NDVI), determined from satellite-based land use data, in the post-monsoon season, indicates the ingression of wastewater-derived OM in groundwater under the urban area. Attenuated protein:humic-like fluorescence in groundwater close to the river points towards the mixing of groundwater and river water. This ingress of surface-derived OM is plausibly exacerbated by intensive groundwater pumping under these areas. Our approach to link the composition of aqueous organics with land use could easily be adapted for similar hydrogeochemical settings to determine the factors controlling groundwater DOM composition in various contexts.

Emerging organic contaminants in the River Ganga and key tributaries in the middle Gangetic Plain, India: Characterization, distribution & controls.

The presence and distribution of emerging organic contaminants (EOCs) in freshwater environments is a key issue in India and globally, particularly due to ecotoxicological and potential antimicrobial resistance concerns. Here we have investigated the composition and spatial distribution of EOCs in surface water along a ∼500 km segment of the iconic River Ganges (Ganga) and key tributaries in the middle Gangetic Plain of Northern India. Using a broad screening approach, in 11 surface water samples, we identified 51 EOCs, comprising of pharmaceuticals, agrochemicals, lifestyle and industrial chemicals. Whilst the majority of EOCs detected were a mixture of pharmaceuticals and agrochemicals, lifestyle chemicals (and particularly sucralose) occurred at the highest concentrations. Ten of the EOCs detected are priority compounds (e.g. sulfamethoxazole, diuron, atrazine, chlorpyrifos, perfluorooctane sulfonate (PFOS), perfluorobutane sulfonate, thiamethoxam, imidacloprid, clothianidin and diclofenac). In almost 50% of water samples, sulfamethoxazole concentrations exceeded predicted no-effect concentrations (PNECs) for ecological toxicity. A significant downstream reduction in EOCs was observed along the River Ganga between Varanasi (Uttar Pradesh) and Begusarai (Bihar), likely reflecting dilution effects associated with three major tributaries, all with considerably lower EOC concentrations than the main Ganga channel. Sorption and/or redox controls were observed for some compounds (e.g. clopidol), as well as a relatively high degree of mixing of EOCs within the river. We discuss the environmental relevance of the persistence of several parent compounds (notably atrazine, carbamazepine, metribuzin and fipronil) and associated transformation products. Associations between EOCs and other hydrochemical parameters including excitation emission matrix (EEM) fluorescence indicated positive, significant, and compound-specific correlations between EOCs and tryptophan-, fulvic- and humic-like fluorescence. This study expands the baseline characterization of EOCs in Indian surface water and contributes to an improved understanding of the potential sources and controls on EOC distribution in the River Ganga and other large river systems.

The complete plastome of Hyacinthoides non-scripta (L.) Chouard ex Rothm. (Asparagaceae).

The whole plastome sequence of Hyacinthoides non-scripta, was assembled and annotated in this study. This is the first complete plastid genome for the genus Hyacinthoides. The plastome is 155,035 bp long and consists of a large single-copy (LSC) region spanning 83,947 bp, a small single-copy (SSC) region spanning 18,496 bp, and two inverted repeat (IR) regions, each of which is 26,296 bp in length. There are 132 genes annotated in the plastome, of which the protein-coding gene infA has pseudogenized.

GSK-3ß dysregulation contributes to parkinson's-like pathophysiology with associated region-specific phosphorylation and accumulation of tau and α-synuclein.

Aberrant posttranslational modifications (PTMs) of proteins, namely phosphorylation, induce abnormalities in the biological properties of recipient proteins, underlying neurological diseases including Parkinson's disease (PD). Genome-wide studies link genes encoding α-synuclein (α-Syn) and Tau as two of the most important in the genesis of PD. Although several kinases are known to phosphorylate α-Syn and Tau, we focused our analysis on GSK-3ß because of its accepted role in phosphorylating Tau and to increasing evidence supporting a strong biophysical relationship between α-Syn and Tau in PD. Therefore, we investigated transgenic mice, which express a point mutant (S9A) of human GSK-3ß. GSK-3ß-S9A is capable of activation through endogenous natural signaling events, yet is unable to become inactivated through phosphorylation at serine-9. We used behavioral, biochemical, and in vitro analysis to assess the contributions of GSK-3ß to both α-Syn and Tau phosphorylation. Behavioral studies revealed progressive age-dependent impairment of motor function, accompanied by loss of tyrosine hydroxylase-positive (TH+ DA-neurons) neurons and dopamine production in the oldest age group. Magnetic resonance imaging revealed deterioration of the substantia nigra in aged mice, a characteristic feature of PD patients. At the molecular level, kinase-active p-GSK-3ß-Y216 was seen at all ages throughout the brain, yet elevated levels of p-α-Syn-S129 and p-Tau (S396/404) were found to increase with age exclusively in TH+ DA-neurons of the midbrain. p-GSK-3ß-Y216 colocalized with p-Tau and p-α-Syn-S129. In vitro kinase assays showed that recombinant human GSK-3ß directly phosphorylated α-Syn at a single site, Ser129, in addition to its known ability to phosphorylate Tau. Moreover, α-Syn and Tau together cooperated with one another to increase the magnitude or rate of phosphorylation of the other by GSK-3ß. Together, these data establish a novel upstream role for GSK-3ß as one of several kinases associated with PTMs of key proteins known to be causal in PD.

[Ultrasound biomicroscopy long-term study of filtering belbs]. / Analyse à long terme de la bulle de filtration après chirurgie de glaucome, par échographie ultrasonore.

PURPOSE: To study aspect of filtering blebs by Ultrasound Biomicroscopy (UBM) and to compare it to intraocular pressure (IOP), to type of surgery performed and to the measurement of the anterior chamber angle after glaucoma surgery. METHODS: An observational study, conducted between January and December 2010 on 46 eyes of 42 patients who underwent glaucoma surgery. 17 combined surgeries (14 non-penetrating deep sclerectomy (NPDS) with phacoemulsification and 3 trabeculectomy with phacoemulsification) and 29 filtering surgeries alone (16 NPDS and 13 trabeculectomy) were performed by the same surgeon with application of mitomycin C for 1.30 minutes during surgery. After surgery, IOP was controlled at day 5, day 30 and at UBM realisation. Filtering blebs were classified according to Yamamoto's study: functional blebs (L: Low-reflective) and non-functional blebs (H: High-reflective, E: Encapsulated and F: Flattened). RESULTS: Mean follow-up was 21 months (± 3.7). We noted a significant decrease in IOP, mean preoperative IOP 23.2mmHg (± 9.4), mean post operative IOP 14.7mmHg (± 3.3) (P<0.001). We identified 36 functional blebs (36L type) and 10 non-functional blebs (including 1 H, 7 F and 2 E). There was no significant morphological differences between filtering blebs after combined surgery and filtering surgery alone (P=0.072). We did not find any morphological difference between filtering blebs after trabeculectomy and NPSD (P=0.394). Blebs are significantly more functional with an IOP less or equal to 6mmHg after surgery (P=0.028). We didn't find any difference between efficacy of filtering blebs and depth of the anterior chamber angle. CONCLUSION: Our study reports 78% of functional blebs after glaucoma surgery (mean duration of 21 months). Type of surgery does not seem to interfere with the long-term morphological type of the bleb, however the immediate postoperative IOP less than or equal to 6mmHg is a factor of good prognosis. UBM appears to be an interesting tool for monitoring patients undergoing glaucoma surgery.

[Vincristine-induced unilateral ptosis: case report and review of the literature]. / Ptosis unilatéral induit par la vincristine : à propos d'un cas et revue de la littérature.

We report the case of a 31-month-old girl, treated by the ifosfamide-vincristine-actinomycin chemotherapy protocol for vaginal rhabdomyosarcoma, who developed a unilateral left ptosis on day 36 of chemotherapy, i.e. 7 days after the fifth vincristine dose (1.5mg/m(2) or 0.90 mg). The cumulative vincristine dose was thus 4.50mg. The remainder of the neurological and systemic examinations were unremarkable. Laboratory testing and thoracic-cervical-cranial CT were normal. Other causes of ptosis were excluded. The ptosis decreased a few days after the infusion of vincristine and re-increased just after a new dose. It finally resolved upon lowering the dose of vincristine. According to our observations, the role of vincristine in the pathogenesis of this ptosis appears "likely". In such cases, maintenance of treatment is possible with adjustment of vincristine doses, but requires regular follow-up.

[Efficacy and tolerability of highly crosslinked hyaluronic acid injections in the management of the enophthalmous orbit]. / Efficacité et tolérance des injections d'acide hyaluronique hautement réticulé dans la prise en charge des énophtalmies.

OBJECTIVE: Evaluation of the efficacy and tolerability of highly crosslinked hyaluronic acid injections in treating the enophthalmous orbit. METHODS: Retrospective study of 11 enophthalmic patients who received an intraorbital injection of Juvederm(®) Voluma between June 2007 and October 2008. The mean follow-up was 19 months (range 12-25 months). RESULTS: Twelve orbits of 11 patients were treated, including nine with post-enucleation socket syndrome (PESS). Volume loss was corrected in 66.67% of cases (eight orbits) with only one intraorbital injection. Two patients requested an additional injection, achieving a final success rate of 83.33%. A rate of 16.67% (two orbits) developed some bruising, mild swelling and hypersensivity at the injection site within 24 hours of administration of the filler, representing minor, temporary side-effects of which the patients had been forewarned. Persistent edema was noted in 16.67% of cases, likely due to an overcorrection of ptosis, and ptosis was exacerbated in 16.67% of cases (two orbits). One ptosis was corrected after several months, with no particular difficulties related to the hyaluronic acid. No additional complications were identified. CONCLUSION: Juvederm(®) Voluma appears to be an effective filler for reduction of enophthalmos with a single intraorbital injection. In our experience, this product seems to have a longer duration of action than reported by the manufacturer and appears to perform like a semi-permanent or even permanent filler.

["Teddy bear granuloma", a rare condition: a case report of a 3-year-old child]. / « Teddy bear granuloma ¼, une pathologie rare : à propos du cas d'un enfant de trois ans.

Conjunctival synthetic fiber granulomas, or "Teddy bear granulomas", are rare granulomatous responses to synthetic fabric fibers. We report the case of a 3-year-old boy with no prior infectious or traumatic history, brought in by his parents for an incidentally discovered conjunctival growth in his right eye. Slit lamp examination revealed a 10-mm growth in the inferior fornix surrounding a small greyish foreign body. Surgical excision and histopathology revealed granulomatous inflammatory cell response with foreign body giant cells surrounding exogenous material. This foreign material was birefringent in polarized light, very suggestive of synthetic fabric fibers, which permitted the diagnosis of Teddy bear granuloma. Synthetic fiber granulomas present in children as unilateral, more or less inflammatory growths in the inferior conjunctival fornix. Surgical excision with histopathology makes the diagnosis and effects the cure.

[Facial necrotizing fasciitis after mild trauma of the eyelid: role of nonsteroidal anti-inflammatory treatment]. / Fasciite nécrosante de la face après un traumatisme palpébral mineur: rôle des anti-inflammatoires.

Facial necrotizing fasciitis is a rare but potentially serious and fatal infection, especially in children. We report the case of a five-year-old girl who developed rapidly progressive necrotizing fasciitis of the face secondary to a mild trauma, with a small wound in the upper eyelid. She had received nonsteroidal anti-inflammatory treatment before she was referred to our hospital. Despite surgical debridement of necrotic tissues and intravenous antibiotic therapy, recurrence occurred. Final progression was satisfactory without sequelae. We discuss here the role of nonsteroidal anti-inflammatory drugs in the development of necrotizing fasciitis in cutaneous lesions, whether traumatic or not.

[Orbital tumors: the ophthalmologist's point of view (biopsies - approaches - exenteration)]. / Les tumeurs de l'orbite : le point de vue de l'ophtalmologiste (biopsies-voies d'abord-exentération).

This publication details the indications and contraindications of orbital tumor biopsies and surgical removal. Until now biopsies of pleomorphic adenomas were contraindicated. This management is now being reconsidered. Contrary to past convention, for suspected malignant tumors, a biopsy is essential. Great caution is required in surgery of inflammatory pseudotumors. Surgery is not recommended in lymphomas.

[Orbital tumors in children: clinical examination, imaging, specific progression]. / Les tumeurs d'orbite de l'enfant : examen clinique, paraclinique, diagnostic et particularités évolutives.

"Orbital tumors (OT) are neoplasms of the bony orbit and contents except for the eyeball." Given this definition, we exclude the retinoblastomas, which are the most frequent tumors of this anatomical area in the pediatric population. Although these tumors are rare, there is a great variety of etiologies. Among them, the most frequent OTs in childhood are rhabdomyosarcomas and metastatic tumors: metastatic neuroblastomas and leukemias (chloromas). Moreover, adult and pediatric varieties of OT are made up of two clusters of distinctive histological entities. Examination must be careful: measurement, direction of proptosis, impairment of ocular motility, compressive optic neuropathy, strabismus, etc. Age at onset as well as unilateral or bilateral proptosis are important features. Benign tumors such as dermoid cysts or hemangiomas grow slowly, whereas rapid growth suggests a malignant tumor. Fundi and visual acuity should be checked. The general examination focuses especially on cutaneous abnormalities such as café au lait spots and subcutaneous nodules in neurofibromatosis type 1 (NF1), a hemangioma that often involves the cutaneous portion of the eyelid. When a metastatic tumor is suspected, abdominal palpation and ultrasonography must be performed. Ultrasonography leaves the posterior third of the orbit inaccessible to exploration. The depth to which it can penetrate the orbit is limited (20mm). Most of the time, standard x-rays, CT, and MR imaging allow for an adequate assessment and usually provide a diagnosis. In children, CT and MRI sometimes require anesthesia to be properly performed.

[Limbal-conjunctival autograft in pterygium surgery]. / L'autogreffe limbo-conjonctivale dans la prise en charge chirurgicale des ptérygions.

INTRODUCTION: The aim of this study was to estimate the efficacy of limbal-conjunctival autograft in the treatment of pterygium. MATERIAL AND METHODS: We conducted a retrospective study including 15 patients (16 eyes) operated on for pterygium by limbal-conjunctival autograft. The examination included the search for risk factors and visual acuity, as well as corneal astigmatism and pterygium measurement. The follow-up included an examination at day 8, 1 month, and 3 months and assessed the integration of the transplant on the eye's surface, the aesthetic aspect, and recurrence. We describe the patients' characteristics, visual acuity, and astigmatism before and after surgery. RESULTS: The mean age of the patients was 56 years (range, 31-81 years). Before surgery, irritative signs and astigmatism, were found in 37% and impaired visual acuity in 81%. The mean duration of the follow-up after surgery was 19 months. Visual acuity and astigmatism improved in 56% of our patients. All transplants and harvest sites had a satisfactory macroscopic aspect. However, one patient suffered from a corneal invasion by fibrovascular tissue, 7 months postoperatively, which remained stable at the end of follow-up. DISCUSSION/CONCLUSION: In our study, the limbal-conjunctival autograft was a safe and effective surgical treatment with a very low recurrence rate at long-term follow-up.

[External dacryocystorhinostomy under local anesthesia and sedation]. / Les dacryocystorhinostomies par voie externe sous anesthésie locale et sédation.

INTRODUCTION: External dacryocystorhinostomy (DCR) surgery is highly advantageous in that it can be performed under local anesthesia associated with sedation. We aimed at verifying the efficiency of the anesthesia, studying the general behavior of the patient and the quality of the surgery. PATIENTS AND METHODS: A prospective study of a local anesthetic protocol associated with sedation was conducted in our Oculoplastic Department on 34 patients (71.5+/-8.3 years of age) between may 2007 and march 2008. The anesthetic protocol consisted of blocking four nerves based on the analysis of the anatomy of facial innervation. The including criteria were patient antecedents such as arterial hypertension, cardiac or lung problems, diabetes, and no contraindications for local anesthesia. The hemodynamic constants, variability of the Ramsay score, and complications such as bleeding or pain were studied. The progress of the surgery was simultaneously evaluated by the patients, anesthesiologists, and surgeons. RESULTS: Both the hemodynamic constants and the Ramsay score remained stable intra- and postoperatively. In addition, the visual analog scale (VAS) scores remained low. Both surgeon and patient satisfaction was excellent (88.4 % of the patients declared that they were ready to choose the same anesthetic protocol if new surgery were to be performed). The surgery's success rate was 79.3 % (no watering at 3 months) versus 82 % for the patients operated under general anesthesia. CONCLUSION: The protocol of local anesthesia associated with sedation for external DCR is therefore safe and efficient.

[CINCA syndrome: a rare cause of papilledema. The case of homozygous twins]. / Une cause rare d'oedème papillaire: le CINCA syndrome. Les cas de jumeaux homozygotes.

CINCA syndrome is an autoinflammatory disease in childhood characterized by multisystemic manifestations: cutaneous, articular, and neurological including sensory organs. We report the case of homozygous twins affected by CINCA syndrome. The diagnosis was evoked on the basis of multiple systemic symptoms (multiple episodes of fever of unknown origin, mental retardation, short stature, meningitis, hearing loss, bilateral papilledema) and confirmed by the presence of a CIAS1 mutation on genetic analysis. After few months of treatment by anakinra (an interleukin-1 receptor antagonist) the children began to grow again and we noted regression of the biological inflammatory syndrome.

Targeting the progression of Parkinson's disease.

By the time a patient first presents with symptoms of Parkinson's disease at the clinic, a significant proportion (50-70%) of the cells in the substantia nigra (SN) has already been destroyed. This degeneration progresses until, within a few years, most of the cells have died. Except for rare cases of familial PD, the initial trigger for cell loss is unknown. However, we do have some clues as to why the damage, once initiated, progresses unabated. It would represent a major advance in therapy to arrest cell loss at the stage when the patient first presents at the clinic. Current therapies for Parkinson's disease focus on relieving the motor symptoms of the disease, these unfortunately lose their effectiveness as the neurodegeneration and symptoms progress. Many experimental approaches are currently being investigated attempting to alter the progression of the disease. These range from replacement of the lost neurons to neuroprotective therapies; each of these will be briefly discussed in this review. The main thrust of this review is to explore the interactions between dopamine, alpha synuclein and redox-active metals. There is abundant evidence suggesting that destruction of SN cells occurs as a result of a self-propagating series of reactions involving dopamine, alpha synuclein and redox-active metals. A potent reducing agent, the neurotransmitter dopamine has a central role in this scheme, acting through redox metallo-chemistry to catalyze the formation of toxic oligomers of alpha-synuclein and neurotoxic metabolites including 6-hydroxydopamine. It has been hypothesized that these feed the cycle of neurodegeneration by generating further oxidative stress. The goal of dissecting and understanding the observed pathological changes is to identify therapeutic targets to mitigate the progression of this debilitating disease.

[Sentinel lymph node biopsy for lymphophilic conjunctival and eyelid tumors: report of 8 cases]. / Biopsie du ganglion sentinelle dans les tumeurs lymphophiles conjonctivales et palpébrales: à propos de 8 cas.

OBJECTIVE: To report our experience in sentinel lymph node biopsy for lymphophilic conjunctival and eyelid tumours. METHODS AND RESULTS: Preliminary study (2005-2007) on 8 patients with conjunctival and or eyelid tumours (melanomas, epidermoid carcinoma, Merkel cell carcinoma). All patients underwent preoperative lymphoscintigraphy 18 FdG pet CT Surgery was performed with complete neck dissection. Sentinel nodes and other nodes harvested were processed separately for histopathologic study; the sentinel were confirmed as histologicaly positive for five patients. Additional positive nodes were found in two out of those five patients. No positive lymph node was found in patients with negative lymphoscintigraphy. After a follow up ranging from 12 to 43 months: two patients died, and 6 are free of disease. CONCLUSIONS: These results demonstrate a very hight level of invaded NO lymph node and confirm the interest of sentinel node technique for optimisation of the therapeutic strategy in lymphophilic conjunctival and eyelid tumours.