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.

THE COVID-19 PANDEMIC LOCKDOWN'S IMPACT ON ROUTINE CHILDHOOD VACCINATION.

The COVID-19 pandemic limits worldwide healthcare access, particularly mandated childhood vaccines. The frequency and mean of purposefully delayed immunizations in infants aged ≤1 year throughout the COVID-19 pandemic in Nineveh, Iraq, were studied. A retrospective observational study of vaccination data in Nineveh, Iraq, was conducted throughout the pre-pandemic period in 2019, the pandemic period in 2020, and comparable months in 2021-2022. The study covered every vaccination administered at ages neonate, 2, 4, 6, 9, and 12 months. The total number of visits mean for the period (Mar-May) 2020 (comprehensive lockdown period) decreased (-18.5%) against (March-May) 2019, and around 2726 children per day were missing immunization. All scheduled vaccines for children aged ≤12 months showed a decrease. The lowest monthly vaccination coverage rate was in March 2020 (61.0%), with the vaccine coverage rate of IPV (70.25%) being the lowest one, then the BCG vaccine at 70.39%, the Pentavalent vaccine at 70.98%, the HBV vaccine at 74.33%, OPV vaccine 79.3%, Measles vaccine (79.45%), and for MMR vaccine 87.34%. The COVID-19 pandemic's significant effects on childhood immunization, recovered in the months that followed but did not reach that before the pandemic in 2019. Intentional vaccination disruption exposes young infants to avoidable infectious illnesses, emphasizing the importance of personalized interventions to improve immunization visits as well as secure the delivery of services.

Gender differences with short-term vs 12 months dual antiplatelet therapy in patients with acute coronary syndrome treated with the COMBO dual therapy stent: 2-years follow-up results of the REDUCE trial.

BACKGROUND: Gender differences in the thrombotic and bleeding risk have been suggested to condition the benefits of antithrombotic therapies in Acute Coronary Syndrome (ACS) patients, and mainly among those undergoing percutaneous coronary interventions with drug eluting stents (DES). The impact of gender on the optimal duration of dual antiplatelet therapy (DAPT) in ACS patients is still unexplored and was, therefore, the aim of the present sub-study. METHODS: REDUCE was a prospective, multicenter, randomized investigator-initiated study designed to enroll 1500 ACS patients after treatment with the COMBO Dual Stent Therapy, based on a noninferiority design. Patients were randomized in a 1:1 fashion to either 3 or 12 months of DAPT. Primary study endpoint was a composite of all-cause mortality, myocardial infarction, definite/probable stent thrombosis (ST), stroke, target-vessel revascularization (TVR) and bleedings (BARC II, III, V) at 12 months. Secondary endpoints were cardiovascular mortality and the individual components of the primary endpoint within 24 months. RESULTS: From June 2014 to May 2016 300 women and 1196 men were included in the study. Among them, 43.7% of females and 51.9% of males were assigned to the 3 months DAPT treatment. Baseline characteristics were well matched between the two arms, with the exception of a lower rate of TIMI flow < 3 (p = 0.04), lower systolic blood pressure (p = 0.05) and use of spironolactone (p = 0.006) among women and a more advanced age (p = 0.05) among men receiving a short-term DAPT. At a mean follow-up of 525 (± 198) days, no difference in the primary endpoint was observed according to DAPT duration in both females [6.9% vs 5.9%, HR (95% CI) = 1.19 (0.48-2.9), p = 0.71] and males [8.2% vs 9%, HR (95% CI) = 0.92 (0.63-1.35), p = 0.67; p INT = 0.20]. Results were confirmed after correction for baseline differences [females: adjusted HR (95% CI) = 1.12 (0.45-2.78), p = 0.81; males: adjusted HR (95% CI) = 0.90 (0.61-1.32), p = 0.60]. Comparable rates of survival, thrombotic (MI, stent thrombosis, TVR, stroke) and bleeding events were observed with the two DAPT strategies, with no impact of gender. CONCLUSIONS: The present study shows that among ACS patients randomized in the REDUCE trial, a 3 months DAPT strategy offers comparable results as compared to a standard 12 months DAPT at 2-years follow-up in both male and female gender.

Binding of the regulatory domain of MutL to the sliding ß-clamp is species specific.

The ß-clamp is a protein hub central to DNA replication and fork management. Proteins interacting with the ß-clamp harbor a conserved clamp-binding motif that is often found in extended regions. Therefore, clamp interactions have -almost exclusively- been studied using short peptides recapitulating the binding motif. This approach has revealed the molecular determinants that mediate the binding but cannot describe how proteins with clamp-binding motifs embedded in structured domains are recognized. The mismatch repair protein MutL has an internal clamp-binding motif, but its interaction with the ß-clamp has different roles depending on the organism. In Bacillus subtilis, the interaction stimulates the endonuclease activity of MutL and it is critical for DNA mismatch repair. Conversely, disrupting the interaction between Escherichia coli MutL and the ß-clamp only causes a mild mutator phenotype. Here, we determined the structures of the regulatory domains of E. coli and B. subtilis MutL bound to their respective ß-clamps. The structures reveal different binding modes consistent with the binding to the ß-clamp being a two-step process. Functional characterization indicates that, within the regulatory domain, only the clamp binding motif is required for the interaction between the two proteins. However, additional motifs beyond the regulatory domain may stabilize the interaction. We propose a model for the activation of the endonuclease activity of MutL in organisms lacking methyl-directed mismatch repair.

Two New and Two Known Species of the Genus Paraoxydirus Jairajpuri and Ahmad, 1978 (Nematoda: Dorylaimida) from Western Ghats of India.

Two new and two known species of the genus Paraoxydirus Jairajpuri and Ahmad, 1978 are described and illustrated from Western Ghats of India. P. vulvalpapillatus n. sp. is characterized by having large sized body (L = 4.6 - 4.8 mm); lip region continuous with completely amalgamated lips; amphidial fovea cup - shaped; 5 - 6 µm long odontostyle; 11 - 13 µm long odontophore; pharyngeal expansion about 28 - 36 % of neck length; transverse vulva; vulval papillae conspicuous; males with 46 - 54 µm long spicules; 11 - 14 continuous ventromedian supplements and long filiform tail similar in both sexes. P. indicus n. sp. is characterized by having large sized body (L = 4.0 - 4.8 mm); lip region poorly offset with amalgamated lips; amphidial fovea cup-shaped; 7 - 8 µm long, robust odontostyle; 17 - 18 µm long odontophore; pharyngeal expansion about 32 - 40 % of neck length; 21 - 26 µm long cardia; longitudinal vulva; 748 - 894 µm long filiform tail; males with 45 - 54 µm long spicules and 12 - 15 continuous ventromedian supplements. P. gigas Jairajpuri, 1964 and P. novus Jairajpuri, 1965 are redescribed based on specimens collected from several localities. A diagnostic Key and compendium to the identification of its eight valid species is provided.

TREATMENT OF CHRONIC APICAL PERIODONTITIS: IN A SINGLE OR MULTIPLE VISITS? (REVIEW).

The article describes the effectiveness of the treatment of chronic apical periodontitis in one visit compared to multiple visits. A systematic review of the literature was conducted analyzing articles published on PubMed, Google scholar, ResearchGate and ScienceDirect between 2011 and 2021, treatment effectiveness was the selected outcome variable. A total of 21 articles were selected, 9 of which were selected for detailed review. Chief question in this article was: which treatment approach is more effective? Cleaning, Shaping, disinfecting and obturating in one visit? Or multiple (two) visit protocol? Chronic Apical Periodontitis is treatable in one visit, if done properly. Chronic Apical Periodontitis is treatable in one visit, if done properly, with proper shaping, disinfection, and proper hermetic obturation of the root canal. Bioceramic sealers showed the highest success rate out of all sealers used, the usage of 3-5.25% sodium hydrochloride and 17% ethylenediaminetetraacetic acid showed favorable results, although photodynamic therapy and ultrasonic activated irrigation showed outstanding results.

Novel two-dimensional silicon-carbon binaries by crystal structure prediction.

The semimetallic bandstructure of graphene and silicene limit their use in functional devices. Mixing silicon and carbon offers a rather unexplored pathway to build semiconducting sheets compatible with current Si-based electronics. We present here a complete theoretical study of the phase diagram of two-dimensional silicon-carbon binaries. To scan the composition range, we employ an ab initio global structural prediction method, complemented by exhaustive enumeration of two-dimensional structure prototypes. We find a wealth of two-dimensional low-energy structures, from standard honeycomb single- and double-layers, passing by dumbbell geometries, to carbon nanosheets bridged by Si atoms. Many of these phases depart from planarity, either through buckling, or by germinating three-dimensional networks with a mixture of sp2 and sp3 bonds. We further characterize the most interesting crystal structures, unveiling a large variety of electronic properties, that could be exploited to develop high-performance electronic devices at the nanoscale.

Woodhouse-Sakati syndrome in a family is associated with a homozygous start loss mutation in the DCAF17 gene.

BACKGROUND: Woodhouse-Sakati syndrome (WSS) is a rare neuroendocrine and ectodermal disorder inherited in an autosomal recessive pattern. The syndrome presents prominent clinical features, including alopecia, neuroendocrine defects, neurological findings and progressive hearing loss. The condition results from mutations in the DCAF17 gene. AIMS: To search for the underlying genetic defect in a Pakistani family with WSS phenotypes. METHODOLOGY: Whole exome sequencing was used to search for the disease-causing variant. RESULTS: Analysis of the exome data revealed a start loss sequence variant (c.1A>G, p.M1?) in DCAF17. CONCLUSION: This variant is predicted to abolish translation of the DCAF17 polypeptide. To our knowledge, this is the first start loss variant identified in the DCAF17.

Two New Species of the Genus Coomansinema Ahmad and Jairajpuri, 1989 (Nematoda: Dorylaimida) with a Key to its Species.

Two new species of the genus Coomansinema Ahmad and Jairajpuri, 1989 are described and illustrated. C. japonicum n. sp. is characterized by having medium size body (L= 1.40 - 1.45 mm); lip region truncate with completely amalgamated lips; amphideal fovea goblet - shaped; 16 - 20 µm long odontostyle; 23 - 25 µm long odontophore; comparatively anterior position of the second pair of pharyngeal glands; amphidelphic female genital system; longitudinal vulva; males with 48 - 54 µm long spicules; 7 - 8 spaced ventromedian supplements and tail long filiform in female and short conoid in male. C. longicaudatum n. sp. is characterized by having medium size body (L= 1.1 - 1.3 mm); lip region truncate, continuous with completely amalgamated lips; amphideal fovea cup - shaped; 16 - 17 µm long odontostyle; 19 - 20 µm long odontophore; comparatively anterior position of the second pair of pharyngeal glands; amphidelphic female genital system; transverse vulva, intestinal - prerectum junction with a tongue - like structure and 210 - 269 µm long filiform tail. A key to its seven valid species is provided.

First direct evidence of involvement of a homozygous loss-of-function variant in the EPS15L1 gene underlying split-hand/split-foot malformation.

Split-hand/split-foot malformation (SHFM) is a severe form of congenital limb deformity characterized by the absence of 1 or more digits and/or variable degree of median clefts of hands and feet. The present study describes an investigation of a consanguineous family of Pakistani origin segregating SHFM in an autosomal recessive manner. Human genome scan using SNP markers followed by whole exome sequencing revealed a frameshift deletion (c.409delA, p.Ser137Alafs*19) in the EPS15L1 gene located on chromosome 19p13.11. This is the first biallelic variant identified in the EPS15L1 gene underlying SHFM. Our findings report the first direct involvement of EPS15L1 gene in the development of human limbs.

Homozygous XYLT2 variants as a cause of spondyloocular syndrome.

Spondyloocular syndrome (SOS) is a rare autosomal recessive, skeletal disorder. Two recent studies have shown that it is the result of biallelic sequence variants in the XYLT2 gene with pleiotropic effects in multiple organs, including retina, heart muscle, inner ear, cartilage, and bone. The XYLT2 gene encodes xylosyltransferase 2, which catalyzes the transfer of xylose (monosaccharide) to the core protein of proteoglycans (PGs) leading to initiating the process of PG assembly. SOS was originally characterized in 2 families A and B of Iraqi and Turkish origin, respectively. Using DNA from affected members of the same 2 families, we performed whole exome sequencing, which revealed 2 novel homozygous missense variants (c.1159C > T, p.Arg387Trp) and (c.2548G > C, p.Asp850His). Our findings extend the body of evidence that SOS is caused by homozygous variants in the XYLT2 gene. In addition, this report has extended the phenotypic description of SOS by adding follow-up data from 5 affected individuals in one of the two families, presented here.

5 Gbps wireless transmission link with an optically pumped uni-traveling carrier photodiode mixer at the receiver.

We report the first demonstration of a uni-traveling carrier photodiode (UTC-PD) used as a 5 Gbps wireless receiver. In this experiment, a 35.1 GHz carrier was electrically modulated with 5 Gbps non-return with zero on-off keying (NRZ-OOK) data and transmitted wirelessly over a distance of 1.3 m. At the receiver, a UTC-PD was used as an optically pumped mixer (OPM) to down-convert the received radio frequency (RF) signal to an intermediate frequency (IF) of 11.7 GHz, before it was down-converted to the baseband using an electronic mixer. The recovered data show a clear eye diagram, and a bit error rate (BER) of less than 10-8 was measured. The conversion loss of the UTC-PD optoelectronic mixer has been measured at 22 dB. The frequency of the local oscillator (LO) used for the UTC-PD is defined by the frequency spacing between the two optical tones, which can be broadly tuneable offering the frequency agility of this photodiode-based receiver.

Defect engineering in 1D Ti-W oxide nanotube arrays and their correlated photoelectrochemical performance.

Understanding the nature of interfacial defects of materials is a critical undertaking for the design of high-performance hybrid electrodes for photocatalysis applications. Theoretical and computational endeavors to achieve this have touched boundaries far ahead of their experimental counterparts. However, to achieve any industrial benefit out of such studies, experimental validation needs to be systematically undertaken. In this sense, we present herein experimental insights into the synergistic relationship between the lattice position and oxidation state of tungsten ions inside a TiO2 lattice, and the respective nature of the created defect states. Consequently, a roadmap to tune the defect states in anodically-fabricated, ultrathin-walled W-doped TiO2 nanotubes is proposed. Annealing the nanotubes in different gas streams enabled the engineering of defects in such structures, as confirmed by XRD and XPS measurements. While annealing under hydrogen stream resulted in the formation of abundant Wn+ (n < 6) ions at the interstitial sites of the TiO2 lattice, oxygen- and air-annealing induced W6+ ions at substitutional sites. EIS and Mott-Schottky analyses indicated the formation of deep-natured trap states in the hydrogen-annealed samples, and predominantly shallow donating defect states in the oxygen- and air-annealed samples. Consequently, the photocatalytic performance of the latter was significantly higher than those of the hydrogen-annealed counterparts. Upon increasing the W content, photoelectrochemical performance deteriorated due to the formation of WO3 crystallites that hindered charge transfer through the photoanode, as evident from the structural and chemical characterization. To this end, this study validates the previous theoretical predictions on the detrimental effect of interstitial W ions. In addition, it sheds light on the importance of defect states and their nature for tuning the photoelectrochemical performance of the investigated materials.

The Electronic Structure of Beryllium Chains.

We present an ab initio theoretical study of quasi one-dimensional beryllium chains, Be N, from an electronic structure perspective for N = 3, 4,···, 12. In particular, linear and cyclic systems were compared by using high-quality coupled-cluster formalism. Both linear and cyclic species were found to be local minima on the corresponding potential energy surface, for all the considered values of N. The linear geometry is the most stable one only in the case of Be4. Several indicators (energy gap, position spread tensor, locality of the molecular orbitals) clearly show that both linear and cyclic one-dimensional structures, unlike three-dimensional bulk beryllium, have a covalent insulating nature.

Exome sequencing revealed a novel splice site variant in the ALX1 gene underlying frontonasal dysplasia.

Frontonasal dysplasia (FND) is a heterogeneous group of disorders characterized by hypertelorism, telecanthus, broad nasal root, wide prominent nasal bridge, short and wide nasal ridge, broad columella and smooth philtrum. To date one X-linked and three autosomal recessive forms of FND have been reported in different ethnic groups. We sought to identify the gene responsible for FND in a consanguineous Pakistani family segregating the disorder in autosomal recessive pattern. Genome-wide homozygosity mapping using 250KNsp array revealed five homozygous regions in the selected affected individuals. Exome sequencing found a novel splice acceptor site variant (c.661-1G>C: NM_006982.2) in ALX1. Sanger sequencing confirmed the correct segregation of the pathogenic variant in the whole family. Our study concludes that the splice site variant identified in the ALX1 gene causes mild form of FND.

Non-fermentative Gram-negative rods bacteremia in children with cancer: a 14-year single-center experience.

PURPOSE: Data on non-fermentative Gram-negative rods (NFGNR) bacteremia in children with malignancies are limited. The aim of this study was to present clinical picture, antimicrobial susceptibility pattern, risk factors for resistance and outcome in NFGNR bacteremia in children with cancer. METHODS: All episodes of NFGNR bacteremia occurring during 2001-2014 in children with cancer in a tertiary-care hospital were retrospectively analyzed. Pseudomonas and Acinetobacter spp. resistant to three or more antibiotic classes and all Stenotrophomonas maltophilia (SM) were defined as multidrug-resistant bacteria (MDR). RESULTS: A total of 80 children (44 males, 0.8-18 years, median 5 years) developed 107 episodes (116 pathogens) of NFGNR bacteremia; Pseudomonas aeruginosa (PA) (51; 43.9%), Acinetobacter baumannii (AB) (21, 18.1%), SM (18, 15.5%); and others (27, 25.2%). The rate of NFGNR bacteremia in children with certain solid tumors (e.g. sarcoma, 12/134 (9.0%)) was comparable to that of hematological malignancies (52/429 (12.2%). Focal infection and septic shock occurred in 16 (14.9%) and four (3.7%) episodes, respectively. Thirty (25.8%) of 116 NFGNR were MDR. The most significant predictors of bacteremia with MDR PA or AB were severe neutropenia (<100 cells/mm3; OR 7.8, p = 0.002), hospital-acquired (OR 16.9, p < 0.0001) and breakthrough (OR 11.2, p < 0.0001) infection. Infection with MDR bacteria was associated with inappropriate empirical therapy. The 30-day mortality was 3/107 (2.8%), all in neutropenic patients with hematological malignancies. CONCLUSIONS: NFGNR bacteremia can present with nonspecific signs or symptoms. MDR NFGNRs are common and compromise treatment options, but mortality is relatively low. Knowledge of local epidemiology, pattern and risk factors for resistance is important to guide empirical therapy.

A Quantum Mechanical Study of the k-j and k'-j' Vector Correlations for the H + LiH → Li + H2 Reaction.

We have characterized the stereodynamics of the H + LiH (v = 0, j = 0-1) reactive collisions leading to H2 formation through the quantum mechanical analysis of the k-j and k'-j' vector correlations that describe the polarization of the reactants and products, respectively. Our results, which cover the collision energy interval between 10-4 and 1 eV, are unexpectedly complex given the apparent simplicity and featureless nature of the potential energy surface for the LiH2 system and point toward the existence of a dynamical barrier connected to the centrifugal barrier. Both reactants and products, in particular the second ones, display strong directional preferences in the cold region that indicate a bias for collinear approaching and departing geometries and are independent of the final state of the products. As more energy is available for the reaction, the polarization of reactants and products becomes weaker and strongly dependent on the final state. While stereodynamical control is feasible and significant in the cold region, its extent becomes negligible for other energetic regimes.

Exome sequencing revealed a novel biallelic deletion in the DCAF17 gene underlying Woodhouse Sakati syndrome.

Woodhouse Sakati syndrome (WSS, MIM 241080) is a rare autosomal recessive genetic condition characterized by alopecia, hypogonadism, hearing impairment, diabetes mellitus, learning disabilities and extrapydamidal manifestations. Sequence variants in the gene DCAF17, encoding nucleolar substrate receptor, were identified as the underlying cause of inherited WSS. Considerable phenotypic heterogeneity exists in WSS with regard to severity, organs involvement and age of onset, both in inter-familial and intra-familial cases. In this study, the genetic characterization of a consanguineous pedigree showing mild features of WSS was performed, followed by structural analysis of truncated protein. Exome sequencing identified a novel single base deletion variant (c.270delA; K90Nfs8*) in third exon of the gene DCAF17 (RefSeq; NM_025000), resulting in a truncated protein. Structural analysis of truncated DCAF17 revealed absence of amino acid residues crucial for interaction with DDB1. Taken together, the data confirmed the single base pair deletion as the underlying cause of this second report of WSS from Pakistan. This signifies the vital yet unexplored role of DCAF17 both in development and maintenance of adult tissues homeostasis.

On the nature of defect states in tungstate nanoflake arrays as promising photoanodes in solar fuel cells.

An electrochemical method is presented to study the nature of the defect states in sub-stoichiometric tungsten oxide nanoflake photoanodes used in water splitting. First, stoichiometric/sub-stoichiometric tungstate nanoflake arrays were deliberately developed via annealing under different atmospheres (air, O2, and H2) in different sequences. UV-Vis diffuse reflectance spectra and Tauc analysis indicated the presence of oxygen vacancies, which was also confirmed via XRD and Raman analysis, with samples annealed in an air/O2 sequence resulting in the most stoichiometric monoclinic structures. A defect sensitivity factor was proposed to explain the nature of defects whether they are deep or shallow. Mott-Schottky analysis was used to confirm the expected defect donor densities, as well as to confirm the nature of the developed oxygen vacancy defect states. The tungstate photoanodes were tested in photoelectrochemical water splitting cells and their photoconversion efficiency was demonstrated and discussed in detail.

A novel homozygous mutation disrupting the initiation codon in the SLURP1 gene underlies mal de Meleda in a consanguineous family.

Mal de Meleda (MDM) is a palmoplantar keratoderma (PPK), characterized by hyperkeratosis of the palms and soles, and keratotic skin lesions. Patients with MDM can develop perioral erythema, keratotic and lichenoid plaques over the joints (including the elbows and knees), nail abnormalities, joint contractures and stiffness, brachydactyly, sclerodactyly, pseudoainhum, and malodorous maceration. MDM is associated with mutations in the SLURP1 gene. We report a consanguineous family in which MDM was inherited in an autosomal recessive manner. Genotyping using microsatellite markers established linkage in the family to the SLURP1 gene, which has been mapped previously to chromosome 8q24.3. Sequence analysis revealed a homozygous missense mutation (c.2T>C, p.Met1Thr) in affected family members. Molecular docking studies using a ZDOCK server predicted disruption of binding of the mutant variant to its target α7-nAChR. This study further supports the previously reported findings that homozygous mutations in the SLURP1 gene cause MDM.