Tag: nevin manimala

Biochem Genet. 2024 Nov 21. doi: 10.1007/s10528-024-10949-5. Online ahead of print.

ABSTRACT

Cervical cancer (CC) remains a real public health problem in low- and middle-income countries, where technical resources and competent personnel are insufficient. Persistent cervix infection by high-risk human papillomavirus (Hr-HPV) is the main cause of CC development. In the current study, we examined the distribution of Hr-HPV in the general healthy Malian population using cervicovaginal self- sampling. A total of 354 women were recruited, with a median age of 34 ± 11.37 years, IQR (27-43). We found that 100% of participants agreed to self-sample at the health center. For result announcement 99.2% expressed their preference to be contacted by cell phone. Furthermore, 100% of study participants showed their willingness to undergo confirmatory CC test in case of Hr-HPV test proved positive, and to receive treatment in the event of the presence of cervical lesions. The overall prevalence of Hr-HPV was 21.2% (95% CI: 17-25.8). HPV31/35/33/52/58 with 11.9% (95% CI: 8.7-15.7) and HPV39/68/56/66 with 5.9% (95% CI: 3.7-8.9) were the most common Hr-HPV subtypes. We noted that Hr-HPV genotypes were more prevalent among women under 25 years, 36.1% (N = 61). In addition, the distribution of Hr-HPV was statistically associated with age, W = 12,374, p = 0.015. Our data showed that 25.3% (N = 19) of Hr-HPV-positive women were tested positive by VIA/VILI. Among the 19 VIA/VILI-positive women, histological examination showed that 4 were CIN1, 4 were CIN2, and 2 were CIN3 grades. In addition, the median age of participants with CIN2 and CIN3 was statistically higher than the median of those with CIN1 grade, 25 years IQR (21-26.75) versus 50 years, IQR (40.25-55), W = 24, p = 0.009. In sum, end-users are very satisfied with the cervicovaginal self-sampling device for identifying HR-HPV genotypes as part of CC screening. In addition, it enables hospital practitioners to take the necessary action after triaging women according to their HR-HPV genotype.

PMID:39570507 | DOI:10.1007/s10528-024-10949-5

J Endocrinol Invest. 2024 Nov 21. doi: 10.1007/s40618-024-02502-3. Online ahead of print.

ABSTRACT

BACKGROUND: Induction of puberty in boys with constitutional delay of growth and puberty (CDGP) through a short course of low-dose testosterone therapy indicates the critical interaction between testosterone and the androgen receptor (AR) during the activation and maturation of the hypothalamic-pituitary-gonadal axis at puberty onset. Previous studies have shown an inverse relationship between the CAG repeat length and the transactivation function or expression level of the AR gene.

OBJECTIVE: We aimed to investigate whether the AR CAG repeat polymorphism has any implications on pubertal delay.

SUBJECTS AND METHODS: Thirty-three male patients with CDGP were enrolled in the study group, while 53 age-matched healthy individuals who had entered puberty on time were included in the control group. The CAG repeat length was determined through direct DNA sequencing analysis.

RESULTS: The median chronological age of boys with CDGP was 14.2 (14.1-14.6) years, compared to 14.2 (13.65-14.8) years for healthy subjects (p = 0.5). In the CDGP group, 22 (66.7%) children had a family history of the condition. There was no significant difference between the groups in terms of AR CAG repeat length (median AR CAG repeat length: 21 (20-24.5) and 20 (20-24), respectively, p = 0.1). However, in boys with CDGP with a similar family history (n = 22), a significantly longer AR CAG repeat length was found compared to the control group (n = 53) (median AR CAG repeat length: 22 (20-25) and 20 (20-24), respectively, p = 0.03). The median AR CAG repeat length in boys without a family history was 21 (20-22) triplets. Although boys with a family history had a slightly longer AR CAG repeat length than those without, the difference was not statistically significant (p = 0.07). Additionally, no significant differences were observed between boys with non-familial CDGP and control subjects (p = 0.8). Furthermore, no significant differences in anthropometric characteristics or hormonal parameters were found when patients with CDGP were categorized by AR CAG repeat length quartiles.

CONCLUSION: This is the first study to investigate the role of AR CAG polymorphism in the etiopathogenesis of CDGP. Our findings suggest that the AR CAG repeat length may be associated with familial CDGP.

PMID:39570490 | DOI:10.1007/s40618-024-02502-3

Mycopathologia. 2024 Nov 21;189(6):102. doi: 10.1007/s11046-024-00908-4.

ABSTRACT

During the last two decades, wound invasive fungal diseases (WIFDs) have reemerged as important causes of mortality and morbidity in military personnel and civilian casualties in war areas. Historically, mycotic infections acquired in combat operations during Vietnam War and were associated with burn wounds. Modern combat related WIFDs are almost exclusively associated with severe traumatic events which encompass blast exposure as the primary mechanism of injury and subsequent extremity amputation and extensive blood loss. Such infections often lead to deep tissue necrosis, long hospitalizations, extensive surgeries, and more severe amputation. Studies of combat related WIFDs among U.S. military personnel in Operation Enduring Freedom (Afghanistan) demonstrated incidence rates of approximately 7% and crude mortality of 8.5%. WIFDs were also seen in U.K. military personnel returning from Afghanistan and are common in the current Ukraine and Gaza conflicts. Mucorales, Aspergillus and Fusarium species are the predominant causes of WIFDs. These molds are opportunistic pathogens which thrive in patients with immune system imbalances following traumatic injury. They are ubiquitous environmental fungi found in a variety of soils but there are significant regional differences depending on the local soil type, vegetation, and climate. The management of WIFDs is complicated by the limited efficacy of current antifungals on many of these environmental species and by emerging antifungal resistance globally. This review provides an overview of the global burden, epidemiology, and clinical features of combat-related fungal infections with the aim to provide a better understanding of the threat posed for wounded Service Members and civilians.

PMID:39570484 | DOI:10.1007/s11046-024-00908-4

Int J Hematol. 2024 Nov 21. doi: 10.1007/s12185-024-03864-3. Online ahead of print.

ABSTRACT

Lenalidomide is an oral immunomodulatory agent approved for the treatment of relapsed/refractory adult T-cell leukemia/lymphoma (ATLL) in Japan. Post-marketing surveillance (PMS) was conducted to confirm its safety and effectiveness. From April 2017 until April 2020, safety data were obtained for 77 patients and effectiveness data for 65 patients (31.2% of patients had progressive disease as the best response to their most recent prior regimen). Forty-nine patients (63.6%) in the safety analysis set experienced an adverse drug reaction (ADR). Grade ≥ 3 ADRs occurred in 42.9%. The most common Grade ≥ 3 ADRs were neutrophil count decreased/neutropenia and platelet count decreased/thrombocytopenia (11.7% each). Serious ADRs occurred in 26 patients. Five patients had previously received allogeneic hematopoietic stem cell transplantation. Among these, one experienced acute graft versus host disease (GvHD) during lenalidomide administration and two responded to lenalidomide. Effectiveness analysis showed that an objective response was achieved in 29.2% of patients. No statistically significant differences were observed in the objective response rates of patients aged < 70 versus those aged ≥ 70 years (33.3% vs 28.0%, respectively; p = 0.6904). No new safety signals were observed in this PMS, and lenalidomide demonstrated a favorable benefit-risk balance in Japanese patients with ATLL.

PMID:39570473 | DOI:10.1007/s12185-024-03864-3

Support Care Cancer. 2024 Nov 21;32(12):813. doi: 10.1007/s00520-024-09023-y.

ABSTRACT

OBJECTIVES: Due to disease- or therapy-associated immunosuppression, oncological patients suffer from significantly higher morbidity and mortality due to infections transmitted by respiratory pathogens such as Streptococcus pneumoniae and influenza virus. Although the German Standing Committee on Vaccination (STIKO) provides specific recommendations for vaccination against these pathogens, there is no data on vaccination rates in this high-risk population.

METHODS: Data from the interventional EVO study were analyzed to provide information on vaccination rates against Streptococcus pneumoniae and influenza virus in oncological patients. Numbers presented in this publication summarize baseline and follow-up data of the control group; thus, data were not influenced by the intervention.

RESULTS: Data of 370 patients were analyzed; 20.5% of patients were treated for hematological malignancies and 79.5% for solid cancer. 28.1% of patients had received vaccination against influenza and 32.2% against Streptococcus pneumoniae; for the latter only 7.3% according recommendations. While vaccination rates where even lower for patients with thoracic carcinoma (influenza 26.7% and Streptococcus pneumoniae 6.0% according to STIKO recommendations), rates in patients with multiple myeloma were remarkably higher (39.0% and 14.6%).

CONCLUSIONS: Despite strong recommendations to vaccinate and the clear clinical need to prevent infections in the vulnerable group of oncological patients, only the minority was vaccinated against Streptococcus pneumoniae or influenza, underlining the urgent need for better vaccination strategies in this high-risk population.

PMID:39570461 | DOI:10.1007/s00520-024-09023-y

Mol Biol Rep. 2024 Nov 21;52(1):6. doi: 10.1007/s11033-024-10086-7.

ABSTRACT

BACKGROUND: Major Human Histocompatibility complex (MHC or HLA in humans) has been associated to autoimmune diseases. However, only statistical phenomenological and no pathogenetic description has been reached after decades. This shows that MHC single locus association studies are probably useless for HLA/diseases association. Extended HLA (class I and class II genes) haplotypes should also be studied conjointly with class III or complement alleles (complotypes). Complotypes in humans are defined as alleles belonging to C2, C4 and Bf (Factor B) genes/proteins (class III). Also, the placing of MHC class I and class II genes close together with complement genes from at least birds to humans shows existence of a strong selection to gather conjointly these loci that fight microbes, help self-maintenance and avoid autoimmunity. In this paper we aim to study Bf alleles in primates in order to rise again interest to study the role of Bf alleles together with other MHC genes in their physiopathology and evolution.

METHODS: Orangutan (Pongo pygmaeus, Popy) cell lines RNA from 6 different individuals were retrotranscribed, PCR amplified, cloned and DNA sequenced in order to study Bf alleles.

RESULTS: A Bf allele identical to that found in chimpanzee (Patr-Bf*A01) and human (rs641153) was found in two of the six studied orangutans: Popy-Bf*A01 and Popy-Bf*A02. This polymorphism is placed in Factor B codon 32 that defines BF*S and Bf*F proteins in man and produce Leu instead of Arg (Bf*S) or Gln (Bf*F). In addition, each new orangutan allele present synonymous differences with each other at codon 25: Popy-Bf*A01 shows ACG while Popy-Bf*A02 bears ACA, both codifying for Thr.

CONCLUSIONS: The selection for about 15 million years (time gap of evolutionary appearance between orangutan and hominids) shows the importance of this particular allele conservation in immune and self defense in primates. The complotypes (Bf,C2 and C4 loci) alleles together with other MHC class I and Cass II loci alleles are often transmitted in block to the germinal line: this indicates that all specific alleles from the MHC different loci may work together to accomplish MHC functions. All MHC loci alleles should be studied together to unveil their physiopathology and also maintenance of specific alleles (like the one described in this paper) for so long time in evolution should be further studied in Bf and the other neighbouring complement loci (C2 and C4).

PMID:39570459 | DOI:10.1007/s11033-024-10086-7

Arch Dermatol Res. 2024 Nov 21;317(1):37. doi: 10.1007/s00403-024-03535-7.

ABSTRACT

Notalgia Paresthetica (NP) is a type of chronic sensory neuropathy characterized by localized itching, pain and dysesthesias including numbness, tingling, burning, coldness, hypo- and hyperesthesia. It is frequently underdiagnosed and thus, there is no established standard of care for treatment. The objective of our study was to evaluate the efficacy of neural therapy in patients with NP. Patients aged 30-60 years with a diagnosis of NP for at least 6 months were included in our study. Intralesional and segmental neural therapy was administered to the patients in five sessions, with one-week intervals between each session. Patients were evaluated with numeric rating scale (NRS) for pain, the PainDETECT Questionnaire for neuropathic pain, the Short Form-12 (SF-12) for quality of life and the 5-D Itch Scale for pruritus. A total of 12 patients diagnosed with NP were included in the study. The median age of the patients included in the study was 45 years (33-59). 58.3% (n = 7) of the patients were female and 41.7% (n = 5) were male. The median duration of pain was 24 (6-60) months. Itching was observed in 75% (n = 9) and hypoesthesia was present in 58.3% (n = 7) of the patients. Comparisons were made with assessment scales before and 3 months after treatment. There was a significant difference in the pre-treatment NRS, PainDETECT Questionnaire, physical component of SF-12 and 5-D itch scale scores compared to post-treatment. Neural therapy represents a promising complementary treatment method for the reduction of pain, neuropathic pain, and pruritus in patients with NP. Furthermore, it has been demonstrated to enhance quality of life.

PMID:39570455 | DOI:10.1007/s00403-024-03535-7

Neurosurg Rev. 2024 Nov 21;47(1):865. doi: 10.1007/s10143-024-03070-z.

ABSTRACT

INTRODUCTION: Although inflammation is closely associated with the pathogenesis of intracranial aneurysm (IA), detailed causal associations remain unclear. This study aimed to investigate the causality between circulating inflammatory molecules (IMs) and IA.

MATERIALS AND METHODS: The bi-directional Mendelian randomization (MR) analysis was conducted using two genome-wide association studies (GWAS) for inflammatory molecules (IMs) from Finnish and Icelandic populations, as well as GWAS datasets of IA cases and controls of European descent. Colocalization analysis was performed to validate MR associations. Subsequently, Venn analysis was conducted to identify the overlapped causalities.

RESULTS: Integrating the findings from two MR models, RANTES was suggestively associated with IA (Finnish model: inverse variance-weighted odds ratio [OR_IVW] (95% confidence interval [95% CI]), 0.86 (0.74-0.99); Icelandic model: 0.80 (0.68-0.94)) and aneurysmal subarachnoid hemorrhage (aSAH) (OR_IVW (95% CI): 0.81 (0.68-0.95) and 0.80 (0.66-0.97) in Finnish and Icelandic models). IA and its subtypes were not associated with any of candidate IMs. However, colocalization analysis failed to identify significant evidence of shared genetic instruments between the exposures and outcomes, except for the MCP3-aSAH pair in the Icelandic model.

CONCLUSIONS: No significant causality was identified between IMs and IA or their subtypes. RANTES is potentially associated with IA and aSAH. Further investigation is warranted to explore the role of IMs in IA development.

PMID:39570436 | DOI:10.1007/s10143-024-03070-z

J Diabetes Investig. 2024 Nov 21. doi: 10.1111/jdi.14340. Online ahead of print.

ABSTRACT

OBJECTIVE: To investigate the risk of biliary diseases in patients with type 2 diabetes mellitus (T2DM) or obesity treated with tirzepatide.

METHODS: Literature searches were performed using the PubMed, Web of Science, Cochrane Library, and CNKI databases until 20 May 2024. Randomized controlled studies (RCTs) investigating the safety of tirzepatide vs placebo/other hypoglycemic drugs in patients with T2DM or obesity were included. The safety outcomes mainly included the incidence of cholelithiasis, pancreatitis, cholecystitis, and gallbladder/biliary diseases. Cochrane Collaboration’s tool for assessing the risk of bias was used to assess the quality of literature. Heterogeneity was evaluated using I² statistics.

RESULTS: A total of 12 high-quality RCTs (involving 12,351 patients) were included. The results of meta-analysis showed that tirzepatide was associated with gallbladder/biliary diseases (RR = 1.52; 95%CI: 1.17-1.98; I² = 0%, P = 0.76) and cholelithiasis (RR = 1.67; 95%CI: 1.14-2.44; I² = 0%, P = 0.95). Subgroup analysis based on the dose of tirzepatide found no dose-response relationship between different doses of tirzepatide and the risk of gallbladder/biliary diseases and cholelithiasis.

CONCLUSIONS: Based on the data currently available, tirzepatide is associated with the development of cholelithiasis in patients. However, the findings from RCTs still need to be further investigated in many post-marketing safety surveillance programs.

PMID:39569606 | DOI:10.1111/jdi.14340

J Orthop Res. 2024 Nov 21. doi: 10.1002/jor.26019. Online ahead of print.

ABSTRACT

Guided growth for correction of rotational deformities has been reported in several preclinical and clinical studies. Different adverse effects, like growth retardation, articular deformities, and rebound effect have been reported. We have tested a novel plate concept (RotOs Plate^TM) intended for the correction of rotational deformities of long bones by guided growth in a porcine model. The plate has sliding screw holes intended to allow for longitudinal growth. Fourteen skeletally immature female pigs were included in the study in a paired design. Mean duration of intervention was 88 days (83-98). CTscans and X-rays were performed at plate insertion and removal. From the CTscans, 3D-models of the left and right femora were made and used for measuring the achieved rotation. Three pigs were excluded for reasons not related to the plate design. The plates rotated as intended in all pigs. In two pigs, there was a cut-out of the proximal screw on the lateral side. Data from these two pigs were included in the results. We observed a mean difference in rotation between the left and right femur of 5.7° in the external direction (CI: 3.7°-7.7°). No statistically significant deformities in the coronal and sagittal plane were observed. The plate worked as intended, that is, the intended rotation was achieved. CLINICAL SIGNIFICANCE: This large animal study shows promising results for the feasibility of the method. It is an important first step in validating the technique and detecting possible adverse effects before clinical studies.

PMID:39569605 | DOI:10.1002/jor.26019