Charting achievements: a two-year retrospective of the society for environmental geochemistry and health (SEGH) and the evolving strategies.

Emerging from the shadow of the COVID-19 pandemic, it is time to ground ourselves and retrospectively assess the recent achievements of SEGH over the past years. This editorial serves as a comprehensive report on the progress made in comparison to the aspirations and goals set by the society's board in 2019 (Watts et al., Environ Geochem Health 42:343-347, 2019) (Fig. 1) and reflects on the state of the SEGH community as it reached its 50th anniversary at the close of 2021 (Watts et al. Environ Geochem Health 45:1165-1171, 2023). The focus lies on how the SEGH community navigated through the extraordinary challenges posed by the COVID-19 pandemic since early 2020, and to what extent the 2023 targets have been met.

Distribution and Pattern of Anti-Tubercular Drug Resistance in Patients with Pulmonary Tuberculosis in Mymensingh Region of Bangladesh.

Globally, the emergence of multidrug-resistant strains of Mycobacterium tuberculosis is an increasing problem that adversely affects patient care and public health. This cross sectional descriptive study was carried out in the Department of Microbiology, Mymensingh Medical College from January 2010 to December 2010 to isolate M. tuberculosis from smear-positive sputum samples by Lowenstein-Jensen (L-J) media and investigate the drug resistance pattern. Among 101 smear-positive cases 80(79.20%) yielded growth of Mycobacteria, 5(4.95%) were contaminated and 16(15.84%) showed no growth. Among 80 isolates 76(95.0%) were M. tuberculosis and the remaining 4(5.0%) were Non-tuberculous Mycobacteria (NTM). Out of 76 M. tuberculosis 27(35.52%) were resistant to at least one drug, 4(5.26%) to Isoniazid (INH), 1(1.32%) to Rifampicin (RMP), 8(10.53%) to Streptomycin (SM) and 0(0.0%) to Ethambutol (EMB) and multi-drug resistant tuberculosis (MDR-TB) was 9(11.84%). The present study creates the impression that fairly high rate of anti-tuberculosis drug resistance among the tuberculosis cases and also high MDR-TB (Resistant to both Rifampicin and Isoniazide). The emergence of MDR-TB poses significant trouble to TB control activities throughout the world. The complexity of MDR-TB operation makes it essential to produce new skills to design, plan, application and monitor interventions for the management of MDR-TB. More surveillance and immediate remedial interventions should be performed to combat the trouble of MDR-TB to the general population.

Long lifetime of bialkali photocathodes operating in high gradient superconducting radio frequency gun.

High brightness, high charge electron beams are critical for a number of advanced accelerator applications. The initial emittance of the electron beam, which is determined by the mean transverse energy (MTE) and laser spot size, is one of the most important parameters determining the beam quality. The bialkali photocathodes illuminated by a visible laser have the advantages of high quantum efficiency (QE) and low MTE. Furthermore, Superconducting Radio Frequency (SRF) guns can operate in the continuous wave (CW) mode at high accelerating gradients, e.g. with significant reduction of the laser spot size at the photocathode. Combining the bialkali photocathode with the SRF gun enables generation of high charge, high brightness, and possibly high average current electron beams. However, integrating the high QE semiconductor photocathode into the SRF guns has been challenging. In this article, we report on the development of bialkali photocathodes for successful operation in the SRF gun with months-long lifetime while delivering CW beams with nano-coulomb charge per bunch. This achievement opens a new era for high charge, high brightness CW electron beams.

Clinical activity at the UK military level 2 hospital in Bentiu, South Sudan during Op TRENTON from June to September 2017.

INTRODUCTION: Diseases and non-battle injuries (DNBIs) are common on UK military deployments, but the collection and analysis of clinically useful data on these remain a challenge. Standard medical returns do not provide adequate clinical information, and clinician-led approaches have been laudable, but not integrated nor standardised nor used long-term. Op TRENTON is a novel UK military humanitarian operation in support of the United Nations Mission in South Sudan, which included the deployment of UK military level 1 and level 2 medical treatment facilities at Bentiu to provide healthcare for UK and United Nations (UN) personnel. METHODS: A service evaluation of patient consultations and admissions at the UK military level 2 hospital was performed using two data sets collected by the emergency department (ED) and medicine (MED) teams. RESULTS: Over a three-month (13-week) period, 286 cases were seen, of which 51% were UK troops, 29% were UN civilians and 20% were UN troops. The ED team saw 175 cases (61%) and provided definitive care for 113 (40%), whereas the MED team saw and provided definitive care for 128 cases (45%). Overall, there were 75% with diseases and 25% with non-battle injuries. The most common diagnoses seen by the ED team were musculoskeletal injuries (17%), unidentified non-malarial undifferentiated febrile illness (UNMUFI) (17%), malaria (13%), chemical pneumonitis (13%) and wounds (8%). The most common diagnoses seen by the MED team were acute gastroenteritis (AGE) (56%), UNMUFI (12%) and malaria (9%). AGE was due to viruses (31%), diarrhoeagenic Escherichia coli (32%), other bacteria (6%) and protozoa (12%). CONCLUSION: Data collection on DNBIs during the initial phase of this deployment was clinically useful and integrated between different departments. However, a standardised, long-term solution that is embedded into deployed healthcare is required. The clinical activity recorded here should be used for planning, training, service development and targeted research.

Infection Prevention and Control Lead Link Practitioner: a new deployed role piloted on Exercise SAIF SAREEA 3.

Disease non-battle injury has plagued British expeditionary forces through the ages. While in recent years significant mortality has reduced, it has had a large impact on operational effectiveness, at times leading to closure of major medical treatment facilities (MTFs).Infection Prevention and Control (IPC) benefits from a subject matter expert and champion to ensure it remains at the front of people's minds and to be on hand to manage acute and dynamic situations. To mitigate the lack of an IPC Nursing Officer, we piloted a deployed military IPC Lead Link Practitioner (IPC-LL) for the first time on a large-scale overseas exercise (SAIF SAREEA 3). An experienced generalist nurse deploying as the IPC-LL (after specific training) provided pre-deployment IPC education and preparation, deployed IPC advice, undertook mandatory audits and monitored IPC compliance throughout the MTFs on the exercise. Data from 22 IPC audits conducted on the exercise showed that the presence of the IPC-LL improved IPC compliance and standards overall in the MTF where based, compared with others. In addition, a gastroenteritis outbreak occurred and was successfully managed with significant input from the IPC-LL. The IPC-LL was also able to add value by pre-empting potential IPC problems from occurring.There is a small pool of deployable Infection Prevention and Control Nursing Officers, so this new IPC-LL role could help to fill the capability gap. The IPC-LL could be the dedicated person focusing on IPC elements, reducing the IPC risk within the deployed field hospital setting where deployed experts are not available.

Copper mediates mitochondrial biogenesis in retinal pigment epithelial cells.

Age related macular degeneration (AMD) is a multifactorial disease with genetic, biochemical and environmental risk factors. We observed a significant increase in copper levels in choroid-RPE from donor eyeballs with AMD. Adult retinal pigment epithelial cells (ARPE19 cells) exposed to copper in-vitro showed a 2-fold increase in copper influx transporter CTR1 and copper uptake at 50 µM concentration. Further there was 2-fold increase in cytochrome C oxidase activity and a 2-fold increase in the mRNA expression of NRF 2 with copper treatment. There was a significant increase in mitochondrial biogenesis markers PGC1ß and TFAM which was confirmed by mitochondrial mass and copy number. On the contrary, in AMD choroid-RPE, the CTR1 mRNA was found to be significantly down-regulated compared to its respective controls. SCO1 and PGC1ß mRNA showed an increase in choroid-RPE. Our study proposes copper to play an important role in mitochondrial biogenesis in RPE cells.

Biological agent in prevention of ocular recurrence in Behçets disease: a case report.

INTRODUCTION: Ocular involvement in Behçets disease (BD) is characterized by recurrent inflammatory attacks leading to poor long-term visual prognosis. The development of biologic agents has heralded a new era in the management of BD uveitis enabling more targeted immune modulation with greater efficacy and has now become the first line agents. OBJECTIVE: To report a case of young gentleman with Behçets disease whose ocular recurrence was controlled with injection Adalimumab. CASE: A 31-year-old male with recurrent oral and genital ulcers with bilateral recurrent uveitis was diagnosed as bilateral ocular Behçet's disease based on positive HLA B51typing and ferning pattern in FFA. He was on oral Prednisolone and Cyclosporine and was advised for biological agents. On presentation to us, he had anterior uveitis with pseudophakia and secondary open angle glaucoma in right eye and posterior sub capsular cataract in left eye. After starting Inj Adalimumab with oral Methotrexate, he ocular inflammation was under control and patient underwent uneventful cataract surgery in left eye. Over 1-year follow-up, the patient is on remission, on injection Adalimumab with the steroid tapered off. CONCLUSION: Biological agents like Adalimumab is effective in controlling recurrences in Behçet's disease.

Ocular distribution of antioxidant enzyme paraoxonase & its alteration in cataractous lens & diabetic retina.

BACKGROUND & OBJECTIVES: The enzyme paraoxonase (PON), an antioxidant enzyme that has both arylesterase and thiolactonase activity, is well studied in cardiovascular diseases. Although a few studies have shown altered PON activity in ocular diseases such as age-related macular degeneration and diabetic retinopathy, but the tissue-wise expression of PON in its three gene forms has not been studied. This study was conducted to see the ocular distribution of PON for any altered expression in ocular pathologies such as in cataract and diabetes mellitus. METHODS: Immunohistochemistry (IHC) of the ocular tissues was done for localizing all three forms of the PON in the human donor eyeballs. The PON arylesterase (PON-AREase) and thiolactonase (PON-HCTLase) activities were determined by spectrophotometry in kinetic mode, and the mRNA expression of the PON genes (PON1-3) was determined by reverse transcription-polymerase chain reaction. RESULTS: IHC showed the presence of both PON1 and 2 in all the ocular tissues and PON3 was seen only in retina. The mRNA expression analysis showed that PON2 and PON3 were present in all the tissues, whereas PON1 was seen only in ciliary and retina. Both the PON-AREase and PON-HCTLase activities were detected in all ocular tissues and was in the order of lens>retina>choroid>ciliary body>iris. The expression and activity were studied in cataractous lens and in diabetic retina of the donor eyes. A significant decrease in PON-AREase activity was seen in cataractous lens (P<0.05) but not in diabetic retina, and there was an increase in PON- HCTLase activity (P<0.05) only in diabetic retina. Bioinformatic studies and in vitro experiments indicated that advanced glycation end products (AGE) such as carboxymethyl -lysine might decrease the PON- AREase activity of the PON. INTERPRETATION & CONCLUSIONS: Distribution of PON enzyme and its activity in ocular tissues is reported here. The study revealed maximal PON activity in lens and retina, which are prone to higher oxidative stress. Differential activities of PON were observed in the lens and retinal tissues from cataractous and diabetic patients, respectively.

Novel identification of Factor XI deficiency in Indian Sahiwal (Bos indicus) cattle.

Factor-XI deficiency (FXID) is inherited as autosomal lethal recessive disorder of carrier Holstein-Friesian bulls. A 76 base pair segment insertion into exon 12 in Factor-XI gene causes FXID in cattle. Keeping this in view the present study was conducted to screen breeding bulls of both indigenous and exotic breeds for mutation in Factor-XI gene and to find out the frequency of FXID carrier animals in breeding bulls. A total of 120 bulls of different age group maintained at Frozen Semen Bull Station, India were randomly selected from different cattle breeds to screen presence of FXID syndrome in breeding sires. Genomic DNA was isolated from blood of the selected bulls. PCR parameters were standardized to obtain 244 and 320 bp amplicons. The results showed that 2 Sahiwal bulls out of 120 animals were carrier for FXID. Amplicons of the carrier animals were sequenced and annoted, which confirms a 76 bp insertion in the exon 12. Bleeding and clotting time showed considerable discrepancy in the carrier animals as compared to the normal animals. The findings of relative mRNA expression of Factor XI transcript revealed identical tendency in the carrier. The frequency of carrier animals and mutant allele was 2.5 % and 0.025 respectively. This study recommends for screening of breeding at AI bull centers in the country for FXID. The study also stands a merit for identification of FXID carrier in Bos indicus for the first time.

Gram-negative bacteraemia; a multi-centre prospective evaluation of empiric antibiotic therapy and outcome in English acute hospitals.

Increasing antibiotic resistance makes choosing antibiotics for suspected Gram-negative infection challenging. This study set out to identify key determinants of mortality among patients with Gram-negative bacteraemia, focusing particularly on the importance of appropriate empiric antibiotic treatment. We conducted a prospective observational study of 679 unselected adults with Gram-negative bacteraemia at ten acute english hospitals between October 2013 and March 2014. Appropriate empiric antibiotic treatment was defined as intravenous treatment on the day of blood culture collection with an antibiotic to which the cultured organism was sensitive in vitro. Mortality analyses were adjusted for patient demographics, co-morbidities and illness severity. The majority of bacteraemias were community-onset (70%); most were caused by Escherichia coli (65%), Klebsiella spp. (15%) or Pseudomonas spp. (7%). Main foci of infection were urinary tract (51%), abdomen/biliary tract (20%) and lower respiratory tract (14%). The main antibiotics used were co-amoxiclav (32%) and piperacillin-tazobactam (30%) with 34% receiving combination therapy (predominantly aminoglycosides). Empiric treatment was inappropriate in 34%. All-cause mortality was 8% at 7 days and 15% at 30 days. Independent predictors of mortality (p <0.05) included older age, greater burden of co-morbid disease, severity of illness at presentation and inflammatory response. Inappropriate empiric antibiotic therapy was not associated with mortality at either time-point (adjusted OR 0.82; 95% CI 0.35-1.94 and adjusted OR 0.92; 95% CI 0.50-1.66, respectively). Although our study does not exclude an impact of empiric antibiotic choice on survival in Gram-negative bacteraemia, outcome is determined primarily by patient and disease factors.

Pattern of Pediatric Uveitis Seen at a Tertiary Referral Center from India.

AIM: To analyze the profile, etiology, complications, medical and surgical management, and visual outcome among pediatric uveitis patients seen at a referral uveitis clinic in India. DESIGN: Retrospective cohort study, tertiary hospital setting. METHODS: Records between January 2007 and April 2010 were reviewed for patients with uveitis who were 0-18 years of age. Uveitis diagnosis was based on SUN criteria; complications, medical and surgical management, and visual outcome were evaluated. RESULTS: Among 190 children with uveitis, 64.2% were boys and 112 had unilateral disease. The median age at presentation was 11 years. Ninety-nine (52%) had anterior, 49 (26%) intermediate, 27 (14%) posterior, and 15 (7.9%) panuveitis. Infectious uveitis was present in 44 patients, of which 21 cases (48%) were posterior uveitis. Parasitic, tuberculous, and viral infectious uveitis was encountered. A total of 174 patients were followed over 315.5 person-years (median = 1.35 years). Seventy-seven (40.5%) children had complications related to uveitis. Forty-six out of 77 complications noted were complicated cataracts. Surgical procedures were done in 46.9% (15%/100 person-years). The visual acuity improved by two Snellen lines in the uveitic eyes, following therapy in 120 children, was stable in 40 children, and worsened in 14 children. Follow-up visual acuity was missing for 16 children. CONCLUSION: A large proportion of pediatric uveitis cases experienced complications of uveitis, mostly prior to presentation for subspecialty management. These often required surgical management, most commonly to clear the visual axis of cataract for visual rehabilitation and to prevent amblyopia. In most cases, tertiary management was associated with visual improvement. The results suggest that subspecialty management can result in improvement of the clinical course of pediatric uveitis.

Reduction in Clostridium difficile environmental contamination by hospitalized patients treated with fidaxomicin.

Fidaxomicin is sporicidal and may be associated with a reduced time to resolution of diarrhoea when used to treat patients with Clostridium difficile infection (CDI). This study investigated whether fidaxomicin for treatment of all patients with CDI reduced C. difficile environmental contamination. Surfaces in the rooms of 66 hospitalized patients treated with metronidazole and/or vancomycin and 68 hospitalized patients treated with fidaxomicin were sampled. Patients treated with fidaxomicin were less likely to contaminate their environment (25/68, 36.8%) than patients treated with metronidazole and/or vancomycin (38/66 57.6%) (P = 0.02). Treatment with fidaxomicin was associated with reduced environmental contamination with C. difficile.

MMP-9 as a potential biomarker for carcinoma of oral cavity: a study in eastern India.

Carcinoma of oral cavity have a high risk of recurrence after initial treatment with surgery, radiotherapy, surgery with adjuvant radiotherapy, or radio-chemotherapy.The present study investigated the changes in expression, activity and regulation of matrix metalloproteinases (MMP) -2 and -9 in oral squamous cell carcinoma (OSCC) which might help to ascertain the invasive potential of the tumor . Tumor tissues and adjacent normal tissues of OSCC patients [N,37; either sex; 20-70 yrs] were subjected to clinico-pathology, histopathology and TNM grading. The enzyme activity and associated signalling was observed with gelatin zymography, immunohistochemistry, ELISA, western blot and semi quantitative reverse transcriptase PCR. OSCC tissues were observed with elevated MMP-9 activity, enhanced expression of fibronectin (FN), phosphorylated focal adhesion kinase (FAK Try 397), phosphatidyl inositol 3­kinase (PI3K), protein kinase B (AKT) and reduced expression of tissue inhibitor of metalloproteinase- 1(TIMP-1) than the control tissues.OSCC patients elicited a predominance of MMP-9 activity via up regulated FAK/PI3K/AKT pathway. A routine MMP-9 analysis may ascertain the invasiveness of the tumor and therefore may be professed as a suitable biomarker for metastatic potential of oral cancer.

A parallel diagnostic accuracy study of three molecular panels for the detection of bacterial gastroenteritis.

Culture-dependent detection of gastroenteric bacteria is labour-intensive and does not provide results in a clinically relevant time frame. Several commercially available multiplex molecular panels are now available which may be more sensitive and could potentially provide rapid results. We compared the diagnostic accuracy, turnaround time and ease of use of three such molecular panels: the RIDA®GENE Bacterial Stool and EHEC/EPEC Panels (R-Biopharm AG, Darmstadt, Germany), the FTD® Bacterial Gastroenteritis Panel (Fast Track Diagnostics, Junglinster, Luxembourg) and the BD MAX™ Enteric Bacterial Panel (Becton Dickinson GmbH, Heidelberg, Germany). The results from 116 retrospective selected and 318 prospective unselected stool samples were compared with conventional culture-based techniques using a gold standard for a positive test of either culture or agreement in two of the three molecular panels. For most targets, the molecular panels were more sensitive than culture, detecting an additional 13 cases that culture missed. The laboratory turnaround time was under 3 h for all molecular panels, compared with 66.5 h for culture. The BD MAX™ panel was the fastest, easiest to use and most flexible.

Targeting STAT3 phosphorylation by neem leaf glycoprotein prevents immune evasion exerted by supraglottic laryngeal tumor induced M2 macrophages.

Tumor-associated macrophages (TAMs) are preferentially M2 skewed and promote tumor growth, angiogenesis, invasion, and/or metastasis. In this study, we have analyzed the in vitro immunomodulatory potential of a non-toxic neem leaf glycoprotein (NLGP) in reprogramming Stage III supraglottic laryngeal tumor cell lysate (SLTCL) induced M2 TAMs to their classical anti-tumor shape (M1). Data generated from this study support that NLGP is effective in preventing the SLTCL induced generation (CD68(+)CD206(+)IL-10(high) to CD68(+)CD206(-)IL-10(low) TAMs) and functions (NO(low) to NO(high), MHC-I(low) to MHC-I(high), CD80(low) to CD80(high)) of pro-tumorous M2 macrophages, which in turn associated with sustained anti-tumor effector functions by promoting cytotoxic T cell activities and suppressing regulatory T cells. Furthermore, our data also suggest that NLGP prevents M2 skewness of TAMs by downregulating phosphorylation of targeted STAT3.